TY - JOUR A1 - Janssen, Jan P. A1 - Hoffmann, Jan V. A1 - Kanno, Takayuki A1 - Nose, Naoko A1 - Grunz, Jan-Peter A1 - Onoguchi, Masahisa A1 - Chen, Xinyu A1 - Lapa, Constantin A1 - Buck, Andreas K. A1 - Higuchi, Takahiro T1 - Capabilities of multi-pinhole SPECT with two stationary detectors for in vivo rat imaging JF - Scientific Reports N2 - We aimed to investigate the image quality of the U-SPECT5/CT E-Class a micro single-photon emission computed tomography (SPECT) system with two large stationary detectors for visualization of rat hearts and bones using clinically available \(^{99m}\)Tc-labelled tracers. Sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR) of the small-animal SPECT scanner were investigated in phantom studies using an ultra-high-resolution rat and mouse multi-pinhole collimator (UHR-RM). Point source, hot-rod, and uniform phantoms with \(^{99m}\)Tc-solution were scanned for high-count performance assessment and count levels equal to animal scans, respectively. Reconstruction was performed using the similarity-regulated ordered-subsets expectation maximization (SROSEM) algorithm with Gaussian smoothing. Rats were injected with similar to 100 MBq [\(^{99m}\)TcTc-MIBI or similar to 150 MBq [\(^{99m}\)Tc]Tc-HMDP and received multi-frame micro-SPECT imaging after tracer distribution. Animal scans were reconstructed for three different acquisition times and post-processed with different sized Gaussian filters. Following reconstruction, CNR was calculated and image quality evaluated by three independent readers on a five-point scale from 1="very poor" to 5="very good". Point source sensitivity was 567 cps/MBq and radioactive rods as small as 1.2 mm were resolved with the UHR-RM collimator. Collimator-dependent uniformity was 55.5%. Phantom CNR improved with increasing rod size, filter size and activity concentration. Left ventricle and bone structures were successfully visualized in rat experiments. Image quality was strongly affected by the extent of post-filtering, whereas scan time did not have substantial influence on visual assessment. Good image quality was achieved for resolution range greater than 1.8 mm in bone and 2.8 mm in heart. The recently introduced small animal SPECT system with two stationary detectors and UHR-RM collimator is capable to provide excellent image quality in heart and bone scans in a rat using standardized reconstruction parameters and appropriate post-filtering. However, there are still challenges in achieving maximum system resolution in the sub-millimeter range with in vivo settings under limited injection dose and acquisition time. KW - small animal SPECT KW - HMDP hydroxymethylene diphosphonate KW - skeletal KW - quality KW - scanner Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230616 VL - 10 ER - TY - JOUR A1 - Hoffmann, Jan V. A1 - Janssen, Jan P. A1 - Kanno, Takayuki A1 - Shibutani, Takayuki A1 - Onoguchi, Masahisa A1 - Lapa, Constantin A1 - Grunz, Jan-Peter A1 - Buck, Andreas K. A1 - Higuchi, Takahiro T1 - Performance evaluation of fifth-generation ultra-high-resolution SPECT system with two stationary detectors and multi-pinhole imaging JF - EJNMMI Physics N2 - Background Small-animal single-photon emission computed tomography (SPECT) systems with multi-pinhole collimation and large stationary detectors have advantages compared to systems with moving small detectors. These systems benefit from less labour-intensive maintenance and quality control as fewer prone parts are moving, higher accuracy for focused scans and maintaining high resolution with increased sensitivity due to focused pinholes on the field of view. This study aims to investigate the performance of a novel ultra-high-resolution scanner with two-detector configuration (U-SPECT5-E) and to compare its image quality to a conventional micro-SPECT system with three stationary detectors (U-SPECT\(^+\)). Methods The new U-SPECT5-E with two stationary detectors was used for acquiring data with \(^{99m}\)Tc-filled point source, hot-rod and uniformity phantoms to analyse sensitivity, spatial resolution, uniformity and contrast-to-noise ratio (CNR). Three dedicated multi-pinhole mouse collimators with 75 pinholes each and 0.25-, 0.60- and 1.00-mm pinholes for extra ultra-high resolution (XUHR-M), general-purpose (GP-M) and ultra-high sensitivity (UHS-M) imaging were examined. For CNR analysis, four different activity ranges representing low- and high-count settings were investigated for all three collimators. The experiments for the performance assessment were repeated with the same GP-M collimator in the three-detector U-SPECT\(^+\) for comparison. Results Peak sensitivity was 237 cps/MBq (XUHR-M), 847 cps/MBq (GP-M), 2054 cps/MBq (UHS-M) for U-SPECT5-E and 1710 cps/MBq (GP-M) for U-SPECT\(^+\). In the visually analysed sections of the reconstructed mini Derenzo phantoms, rods as small as 0.35 mm (XUHR-M), 0.50 mm (GP-M) for the two-detector as well as the three-detector SPECT and 0.75 mm (UHS-M) were resolved. Uniformity for maximum resolution recorded 40.7% (XUHR-M), 29.1% (GP-M, U-SPECT5-E), 16.3% (GP-M, U-SPECT\(^+\)) and 23.0% (UHS-M), respectively. UHS-M reached highest CNR values for low-count images; for rods smaller than 0.45 mm, acceptable CNR was only achieved by XUHR-M. GP-M was superior for imaging rods sized from 0.60 to 1.50 mm for intermediate activity concentrations. U-SPECT5-E and U-SPECT+ both provided comparable CNR. Conclusions While uniformity and sensitivity are negatively affected by the absence of a third detector, the investigated U-SPECT5-E system with two stationary detectors delivers excellent spatial resolution and CNR comparable to the performance of an established three-detector-setup. KW - small-animal imaging KW - SPECT KW - mouse KW - ollimator KW - post-reconstruction filtering Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230361 VL - 7 ER - TY - JOUR A1 - Fecher, David A1 - Hofmann, Elisabeth A1 - Buck, Andreas A1 - Bundschuh, Ralph A1 - Nietzer, Sarah A1 - Dandekar, Gudrun A1 - Walles, Thorsten A1 - Walles, Heike A1 - Lückerath, Katharina A1 - Steinke, Maria T1 - Human Organotypic Lung Tumor Models: Suitable For Preclinical \(^{18}\)F-FDG PET-Imaging JF - PLoS ONE N2 - Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and –testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose positron emission tomography (FDG-PET) these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future. KW - lung and intrathoracic tumors KW - trachea KW - adenocarcinoma of the lung KW - cancer treatment KW - secondary lung tumors KW - pulmonary imaging KW - extracellular matrix KW - collagens Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179678 VL - 11 IS - 8 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Beykan, Seval A1 - Higuchi, Takahiro A1 - Lückerath, Katharina A1 - Weich, Alexander A1 - Scheurlen, Michael A1 - Bluemel, Christina A1 - Herrmann, Ken A1 - Buck, Andreas K. A1 - Lassmann, Michael A1 - Lapa, Constantin A1 - Hänscheid, Heribert T1 - The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy JF - Oncotarget N2 - Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3­clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy. KW - renal scintigraphy KW - neuroendocrine tumor KW - 177Lu KW - MAG3 KW - PRRT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177318 VL - 7 IS - 27 ER - TY - JOUR A1 - Lapa, Constantin A1 - Reiter, Theresa A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Werner, Rudolf A. A1 - Pelzer, Theo A1 - Pizarro, Carmen A1 - Skowasch, Dirk A1 - Thomas, Lena A1 - Schlesinger-Irsch, Ulrike A1 - Thomas, Daniel A1 - Bundschuh, Ralph A. A1 - Bauer, Wolfgang R. A1 - Gartner, Florian C. T1 - Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI JF - Oncotarget N2 - Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series. KW - sarcoidosis KW - PET KW - SSTR KW - somatostatin receptor KW - DOTATOC Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175423 VL - 7 IS - 47 ER - TY - JOUR A1 - Brumberg, Joachim A1 - Beckl, Melanie A1 - Dierks, Alexander A1 - Schirbel, Andreas A1 - Krebs, Markus A1 - Buck, Andreas A1 - Kübler, Hubert A1 - Lapa, Constantin A1 - Seitz, Anna Katharina T1 - Detection Rate of \(^{68}\)Ga-PSMA Ligand PET/CT in Patients with Recurrent Prostate Cancer and Androgen Deprivation Therapy JF - Biomedicines N2 - Prostate-specific membrane antigen (PSMA) ligand PET/CT enables the localization of tumor lesions in patients with recurrent prostate cancer, but it is unclear whether androgen deprivation therapy (ADT) influences diagnostic accuracy. The aim of this study was to evaluate the effect of ADT on the detection rate of \(^{68}\)Ga-PSMA ligand PET/CT. Thus, 399 patients with initial radical prostatectomy and 68Ga-PSMA ligand PET/CT during PSA relapse were retrospectively evaluated. Propensity score matching was used to create two balanced groups of 62 subjects who either did or did not receive ADT within six months before imaging. All \(^{68}\)Ga-PSMA ligand PET/CT were evaluated visually and with semiquantitative measures. The detection rate of tumor recurrence was significantly higher in the group with ADT (88.7% vs. 72.6%, p = 0.02) and improved with increasing PSA-levels in both groups. In subjects with pathological PET/CT and ADT, whole-body total lesion PSMA (p < 0.01) and PSMA-derived tumor volume (p < 0.01) were significantly higher than in those without ADT. More PSMA-positive lesions and higher PSMA-derived volumetric parameters in patients with ADT suggest that a better detection rate is related to a (biologically) more advanced disease stage. Due to high detection rates in patients with PSA-levels < 2 ng/mL, the withdrawal of ADT before PSMA ligand PET/CT cannot be recommended. KW - 68Ga-PSMA ligand PET/CT KW - androgen deprivation therapy KW - detection rate KW - recurrent prostate cancer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219301 SN - 2227-9059 VL - 8 IS - 11 ER - TY - JOUR A1 - Chifu, Irina A1 - Heinze, Britta A1 - Fuss, Carmina T. A1 - Lang, Katharina A1 - Kroiss, Matthias A1 - Kircher, Stefan A1 - Ronchi, Cristina L. A1 - Altieri, Barbara A1 - Schirbel, Andreas A1 - Fassnacht, Martin A1 - Hahner, Stefanie T1 - Impact of the Chemokine Receptors CXCR4 and CXCR7 on Clinical Outcome in Adrenocortical Carcinoma JF - Frontiers in Endocrinology N2 - Chemokine receptors have a negative impact on tumor progression in several human cancers and have therefore been of interest for molecular imaging and targeted therapy. However, their clinical and prognostic significance in adrenocortical carcinoma (ACC) is unknown. The aim of this study was to evaluate the chemokine receptor profile in ACC and to analyse its association with clinicopathological characteristics and clinical outcome. A chemokine receptor profile was initially evaluated by quantitative PCR in 4 normal adrenals, 18 ACC samples and human ACC cell line NCI-H295. High expression of CXCR4 and CXCR7 in both healthy and malignant adrenal tissue and ACC cells was confirmed. In the next step, we analyzed the expression and cellular localization of CXCR4 and CXCR7 in ACC by immunohistochemistry in 187 and 84 samples, respectively. These results were correlated with clinicopathological parameters and survival outcome. We detected strong membrane expression of CXCR4 and CXCR7 in 50% of ACC samples. Strong cytoplasmic CXCR4 staining was more frequent among samples derived from metastases compared to primaries (p=0.01) and local recurrences (p=0.04). CXCR4 membrane staining positively correlated with proliferation index Ki67 (r=0.17, p=0.028). CXCR7 membrane staining negatively correlated with Ki67 (r=−0.254, p=0.03) but positively with tumor size (r=0.3, p=0.02). No differences in progression-free or overall survival were observed between patients with strong and weak staining intensities for CXCR4 or CXCR7. Taken together, high expression of CXCR4 and CXCR7 in both local tumors and metastases suggests that some ACC patients might benefit from CXCR4/CXCR7-targeted therapy. KW - chemokine receptor KW - prognosis KW - adrenocortical carcinoma KW - CXCR4 KW - CXCR7 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216494 SN - 1664-2392 VL - 11 ER - TY - JOUR A1 - Reiners, Christoph A1 - Schneider, Rita A1 - Platonova, Tamara A1 - Fridman, Mikhail A1 - Malzahn, Uwe A1 - Mäder, Uwe A1 - Vrachimis, Alexis A1 - Bogdanova, Tatiana A1 - Krajewska, Jolanta A1 - Elisei, Rossella A1 - Vaisman, Fernanda A1 - Mihailovic, Jasna A1 - Costa, Gracinda A1 - Drozd, Valentina T1 - Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey JF - Frontiers in Endocrinology N2 - Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.” KW - differentiated thyroid carcinoma KW - radioiodine therapy KW - iodine-131 KW - long-term complications KW - young females KW - childhood and adolescence KW - second primary malignancy KW - breast cancer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207766 SN - 1664-2392 VL - 11 ER - TY - JOUR A1 - Hartrampf, Philipp E. A1 - Heinrich, Marieke A1 - Seitz, Anna Katharina A1 - Brumberg, Joachim A1 - Sokolakis, Ioannis A1 - Kalogirou, Charis A1 - Schirbel, Andreas A1 - Kübler, Hubert A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Krebs, Markus T1 - Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy — Do Different Software Solutions Deliver Comparable Results? JF - Journal of Clinical Medicine N2 - (1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: \(^{68}\)Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland–Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible. KW - prostate-specific membrane antigen (PSMA) KW - metabolic tumour volume (MTV) KW - total lesion PSMA KW - biomarker KW - software KW - comparability KW - agreement Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205893 SN - 2077-0383 VL - 9 IS - 5 ER - TY - JOUR A1 - Palmisano, Chiara A1 - Brandt, Gregor A1 - Vissani, Matteo A1 - Pozzi, Nicoló G. A1 - Canessa, Andrea A1 - Brumberg, Joachim A1 - Marotta, Giorgio A1 - Volkmann, Jens A1 - Mazzoni, Alberto A1 - Pezzoli, Gianni A1 - Frigo, Carlo A. A1 - Isaias, Ioannis U. T1 - Gait Initiation in Parkinson’s Disease: Impact of Dopamine Depletion and Initial Stance Condition JF - Frontiers in Bioengineering and Biotechnology N2 - Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson’s disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment. KW - gait initiation KW - Parkinson’s disease KW - basal ganglia KW - dopamine KW - base of support KW - anthropometric measurements Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200801 SN - 2296-4185 VL - 8 ER - TY - JOUR A1 - Lapa, Constantin A1 - Schreder, Martin A1 - Schirbel, Andreas A1 - Samnick, Samuel A1 - Kortüm, Klaus Martin A1 - Herrmann, Ken A1 - Kropf, Saskia A1 - Einsele, Herrmann A1 - Buck, Andreas K. A1 - Wester, Hans-Jürgen A1 - Knop, Stefan A1 - Lückerath, Katharina T1 - [\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values JF - Theranostics N2 - Chemokine (C-X-C motif) receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer including multiple myeloma (MM). Proof-of-concept of CXCR4-directed radionuclide therapy in MM has recently been reported. This study assessed the diagnostic performance of the CXCR4-directed radiotracer [\(^{68}\)Ga]Pentixafor in MM and a potential role for stratifying patients to CXCR4-directed therapies. Thirty-five patients with MM underwent [\(^{68}\)Ga]Pentixafor-PET/CT for evaluation of eligibility for endoradiotherapy. In 19/35 cases, [\(^{18}\)F]FDG-PET/CT for correlation was available. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with standard clinical parameters of disease activity. [\(^{68}\)Ga]Pentixafor-PET detected CXCR4-positive disease in 23/35 subjects (66%). CXCR4-positivity at PET was independent from myeloma subtypes, cytogenetics or any serological parameters and turned out as a negative prognostic factor. In the 19 patients in whom a comparison to [\(^{18}\)F]FDG was available, [\(^{68}\)Ga]Pentixafor-PET detected more lesions in 4/19 (21%) subjects, [\(^{18}\)F]FDG proved superior in 7/19 (37%). In the remaining 8/19 (42%) patients, both tracers detected an equal number of lesions. [\(^{18}\)F]FDG-PET positivity correlated with [\(^{68}\)Ga]Pentixafor-PET positivity (p=0.018). [\(^{68}\)Ga]Pentixafor-PET provides further evidence that CXCR4 expression frequently occurs in advanced multiple myeloma, representing a negative prognostic factor and a potential target for myeloma specific treatment. However, selecting patients for CXCR4 directed therapies and prognostic stratification seem to be more relevant clinical applications for this novel imaging modality, rather than diagnostic imaging of myeloma. KW - medicine KW - multiple myeloma KW - FDG KW - molecular imaging KW - CXCR4 KW - PET KW - radionuclide therapy KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172106 VL - 7 IS - 1 ER - TY - JOUR A1 - Lapa, Constantin A1 - Herrmann, Ken A1 - Schirbel, Andreas A1 - Hänscheid, Heribert A1 - Lückerath, Katharina A1 - Schottelius, Margret A1 - Kircher, Malte A1 - Werner, Rudolf A. A1 - Schreder, Martin A1 - Samnick, Samuel A1 - Kropf, Saskia A1 - Knop, Stefan A1 - Buck, Andreas K. A1 - Einsele, Hermann A1 - Wester, Hans-Juergen A1 - Kortüm, K. Martin T1 - CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma JF - Theranostics N2 - C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted. KW - medicine KW - multiple myeloma KW - PET KW - CXCR4 KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172095 VL - 7 IS - 6 ER - TY - JOUR A1 - Lapa, Constantin A1 - Garcia-Velloso, Maria J. A1 - Lückerath, Katharina A1 - Samnick, Samuel A1 - Schreder, Martin A1 - Otero, Paula Rodriguez A1 - Schmid, Jan-Stefan A1 - Herrmann, Ken A1 - Knop, Stefan A1 - Buck, Andreas K. A1 - Einsele, Hermann A1 - San-Miguel, Jesus A1 - Kortüm, Klaus Martin T1 - \(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions JF - Theranostics N2 - \(^{11}\)C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to \(^{18}\)F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM. KW - medicine KW - PET/CT KW - \(^{11}\)C-methionine KW - multiple myeloma KW - FDG Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172038 VL - 7 IS - 11 ER - TY - THES A1 - Eißler, Christoph Marcel T1 - Assessment of the left ventricular systolic and diastolic function in rats using electrocardiogram-gated cardiac positron emission tomography T1 - Bestimmung der linksventrikulären systolischen und diastolischen Funktion in Ratten durch Elektrokardiogramm-getriggerte kardiale Positronen-Emissions-Tomographie N2 - DD is a cardiac disturbance, which has gained increasing importance in recent years due to its important role in different cardiac disease and cardiomyopathies including ischemic cardiomyopathy, arterial hypertension and diabetic cardiomyopathy. ECG-gated 18F-FDG PET is an imaging technique, that can distinguish between districts of myocardial viability and myocardial scars and further provides information of great interest on the efficacy of experimental approaches designed to improve the cardiac function and/or myocardial metabolism in experimental small animal models. However, ECG-gated 18F-FDG PET is a technique whose feasibility in the assessment of the LV diastolic function in small animals has not been a subject of study. In this thesis, the ability of the ECG-gated 18F-FDG PET for the assessment of both the systolic and diastolic function in eight control rats and in seven ZDF rats, which are an experimental animal model mimicking T2DM conditions and diabetic related complications in humans including DCM, has been investigated The ECG-gated 18F-FDG PET imaging was performed under hyperinsulinemic-euglycemic clamping and the data were stored in list mode files and retrospectively reconstructed. The systolic and diastolic parameters were achieved from the time/volume and the time/filling curve calculated from the software HFV. Additionally, the influence of the number of gates per cardiac cycle on the LV volumes and function parameters has been studied. Hyperinsulinemic-euglycemic clamp procedure and blood glucose measurement did confirm the development of a manifest diabetes in the ZDF rats at the timepoint of the experiments. Regarding the systolic parameters, no significant difference could be detected between the ZDF and ZL rats. The values for the CO were similar in both groups, which demonstrates a similar LV systolic function in the ZDF and the ZL rats at the age of 13 weeks. Values for the systolic parameters are in good line with previous PET, MRI and cardiac catheterization-based studies in diabetic rats. The main finding of this study was that by using in vivo ECG-gated 18F-FDG PET and the software HFV, reliable diastolic parameters could be calculated. Moreover, it was possible to detect the presence of a mild impaired diastolic filling in the ZDF rats in absence of any systolic alteration. This impaired diastolic function in an early stage of diabetes could also be detected by other investigators, who used echocardiography or cardiac catheterization. Therefore, this is the first study showing, that the assessment of the diastolic function in rats can be carried out by ECG-gated 18F-FDG PET imaging. In conclusion, additionally to calculating LV volumes and LV EF, ECG-gated 18F-FDG PET can evaluate the diastolic function of healthy and diabetic rats and is able to detect a DD in ZDF rats. N2 - Die DD ist eine Störung der Herzdynamik, welche, aufgrund ihrer Beteiligung in verschiedenen Herzerkrankungen und Kardiomyopathien wie der ischämischen Kardiomyopathie, der arteriellen Hypertonie und der diabetischen Kardiomyopathie, in den letzten Jahren zunehmend in das Interessenzentrum der Herzforschung gerückt ist. Die EKG-getriggerte 18F-FDG PET ist eine Bildgebungsmethode, welche die Unterscheidung von vitalem Myokard und Narben ermöglicht und zusätzlich noch in der Lage ist, wichtige Informationen zu erheben, welche von Bedeutung für die Beurteilung von experimentelle Behandlungen zur Verbesserung der Herzfunktion und/oder des kardialen Stoffwechsels in präklinischen Tiermodellen sind. Trotz dieser Möglichkeiten wurde bisher noch nicht die Fähigkeit der EKG-getriggerten 18F-FDG PET zur Bestimmung der LV diastoischen Funktion in Kleintiermodellen untersucht. Deshalb wurde in dieser Arbeit das Potential der EKG-getriggerten 18F-FDG PET in Bezug auf die Bestimmung der LV systolischen und diastolischen Funktion in acht Kontrollratten (ZL) und sieben ZDF-Ratten, welche eine experimentelles Tiermodell für T2DM und die damit verbundenen Komplikationen einschließlich der diabetischen Kardiomyopathie sind, untersucht. Die EKG-getriggerte 18F-FDG PET wurde unter der hyperinsulinämischen euglykämischen Klemm Methode durchgeführt, die Daten in „list-mode“ Dateien gespeichert und retrospektiv rekonstruiert. Die Berechnung der LV systolischen und diastolischen Parameter erfolge aus der Zeit-Volumen-Kurve und der Zeit-Füllungs-Kurve durch das Programm HFV. Zudem wurde der Einfluss der pro Rekonstruktion verwendeten „frames“ pro kardialen Zyklus auf die LV Volumina und die linksventrikulären Funktionsparameter untersucht. Durch die hyperinsulinämische euglykämische Klemm Methode und durch Blutglukose Messungen konnte die Entwicklung eines manifesten Diabetes zum Zeitpunkt der Experimente in den ZDF Ratten nachgewiesen werden. Es konnte kein signifikanter Unterschied zwischen den systolischen Parametern der ZDF und der ZL Ratten gefunden werden. Der kardiale Auswurf war nahezu identisch in den beiden Gruppen zum Zeitpunkt der Experimente, was eine vergleichbare systolische Funktion in beiden Gruppen demonstriert. Die erhobenen Werte für die systolischen Parameter befinden sich in guter Übereinstimmung mit den Werten der Literatur von vorherigen PET, MRT und Katheter-gestützten Experimenten in diabetischen Rattenmodellen. Ein wichtiges Ergebnis dieser Arbeit ist die Erhebung von verlässlichen diastolischen Parametern durch den kombinierten Einsatz von EKG-getriggerter 18F-FDG PET und HFV. Zudem war es möglich, eine gestörte diastolische Füllung des LV in den ZDF Ratten nachzuweisen, in Abwesenheit von systolischen Funktionseinschränkungen. Eine Beeinträchtigung der diastolischen Funktion in der frühen Phase des Diabetes wurde bereits in anderen Rattenstudien mittels Echokardiografie und Katheter basierten Untersuchungen gezeigt. Dennoch ist dies hier die erste Studie, welche demonstriert, dass die Bestimmung der diastolischen Funktion auch mit Hilfe der EKG-getriggerten 18F-FDG PET durchgeführt werden kann. In Zusammenfassung lässt sich festhalten, das zusätzlich zu der Bestimmung der LV-Volumina und der LVEF durch EKG-getriggerten 18F-FDG PET auch die Bestimmung der diastolischen Funktion in gesunden und diabetischen Ratten möglich ist und dass durch EKG-getriggerten 18F-FDG PET die Identifikation einer DD in ZDF Ratten möglich ist. KW - Positronen-Emissions-Tomografie KW - preclinical PET KW - ECG-gated PET KW - diastolic dysfunction KW - diabetic cardiomyopathy KW - HFpEF Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219765 ER - TY - JOUR A1 - Da Vià, Matteo Claudio A1 - Solimando, Antonio Giovanni A1 - Garitano-Trojaola, Andoni A1 - Barrio, Santiago A1 - Munawar, Umair A1 - Strifler, Susanne A1 - Haertle, Larissa A1 - Rhodes, Nadine A1 - Vogt, Cornelia A1 - Lapa, Constantin A1 - Beilhack, Andreas A1 - Rasche, Leo A1 - Einsele, Hermann A1 - Kortüm, K. Martin T1 - CIC Mutation as a Molecular Mechanism of Acquired Resistance to Combined BRAF‐MEK Inhibition in Extramedullary Multiple Myeloma with Central Nervous System Involvement JF - The Oncologist N2 - Combined MEK‐BRAF inhibition is a well‐established treatment strategy in BRAF‐mutated cancer, most prominently in malignant melanoma with durable responses being achieved through this targeted therapy. However, a subset of patients face primary unresponsiveness despite presence of the activating mutation at position V600E, and others acquire resistance under treatment. Underlying resistance mechanisms are largely unknown, and diagnostic tests to predict tumor response to BRAF‐MEK inhibitor treatment are unavailable. Multiple myeloma represents the second most common hematologic malignancy, and point mutations in BRAF are detectable in about 10% of patients. Targeted inhibition has been successfully applied, with mixed responses observed in a substantial subset of patients mirroring the widespread spatial heterogeneity in this genomically complex disease. Central nervous system (CNS) involvement is an extremely rare, extramedullary form of multiple myeloma that can be diagnosed in less than 1% of patients. It is considered an ultimate high‐risk feature, associated with unfavorable cytogenetics, and, even with intense treatment applied, survival is short, reaching less than 12 months in most cases. Here we not only describe the first patient with an extramedullary CNS relapse responding to targeted dabrafenib and trametinib treatment, we furthermore provide evidence that a point mutation within the capicua transcriptional repressor (CIC) gene mediated the acquired resistance in this patient. KW - Multiple myeloma KW - Extramedullary disease KW - Capicua transcriptional repressor KW - Drug resistance KW - BRAF mutation Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219549 VL - 25 IS - 2 ER - TY - THES A1 - Saam, Marian T1 - In-vitro-Untersuchung zum Einfluss von Therapeutika auf die PSMA- und CXCR4-Rezeptorexpression in humanen Prostatakarzinomzelllinien T1 - Effect of therapeutic agents an PSMA- and CXCR4-receptorexpression: In-vitro-study of human prostate cancer cell lines N2 - Die therapeutischen Möglichkeiten des metastasierten Prostatakarzinoms (Pca) haben sich durch die neuen Substanzen Docetaxel und Abirateron deutlich verbessert. Das prostataspezifische Membranantigen (PSMA) stellt für die Diagnose und Therapie des Pca´s einen vielversprechenden Angriffspunkt dar. PSMA wird in Prostatakarzinomzellen überexprimiert und dient als Zielstruktur für nicht-invasives bildgebendes Verfahren und Lutetium-177-PSMA-Radioligandentherapie als Therapieoption. Der CXCR4-Rezeptor wird an unterschiedlichen Zelltypen und Organen exprimiert. Seine Überexpression wird mit einer Metastasierung und schlechter Prognose assoziiert. Gallium-68-PSMA PET/CT liefert genaue Kenntnisse bezüglich Ausbreitung und Fortschreiten des Tumorgeschehens. Die vorliegende Arbeit untersucht die Zusammenhänge zwischen Expression von PSMA und CXCR4 in Verbindung mit etablierten Therapeutika und versucht Wege aufzuzeichnen, welche durch Erhöhung der PSMA-Expression zur verbesserten Sensitivität des PSMA PET/CT führen könnten, wodurch der personalisierte Therapieansatz weiter optimiert werden kann. N2 - Novel therapeutic agents such as docetaxel and abiraterone have significantly improved treatment strategies for metastatic prostate cancer in recent years. Prostate-specific membrane antigen (PSMA) represents a promising target for diagnosis and therapy of prostate cancer. PSMA is over expressed in prostate cancer cells providing a target structure for non-invasive imaging and Lutetium-177-PSMA radioligand therapy. The CXCR4-receptor is expressed on different cell types and organs. Its over expression is associated with metastasis and poor prognosis. PET/CT imaging with Gallium-68-labelled PSMA ligands provide relevant information regarding tumor staging and progression. The present study investigates the interaction between expression of PSMA and CXCR4 considering established therapeutic agents to improve sensitivity of PSMA PET/CT imaging and optimize personalized cancer medicine. KW - psma KW - CXCR4 KW - PET/CT KW - PSMA-Rezeptorexpression KW - CXCR4-Rezeptorexpression KW - Prostatakarzinom KW - PET/CT imaging KW - Gallium-68 PET/CT Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219163 ER - TY - JOUR A1 - Schumann, Sarah A1 - Scherthan, Harry A1 - Frank, Torsten A1 - Lapa, Constantin A1 - Müller, Jessica A1 - Seifert, Simone A1 - Lassmann, Michael A1 - Eberlein, Uta T1 - DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [\(^{68}\)Ga]Ga-PSMA I&T JF - Cancers N2 - The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity. KW - DNA double-strand breaks KW - γ-H2AX KW - 53BP1 KW - nuclear medicine KW - dosimetry KW - Ga-68 KW - PSMA KW - PET/CT KW - contrast agent KW - prostate cancer Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200585 SN - 2072-6694 VL - 12 IS - 2 ER - TY - JOUR A1 - Buck, Andreas A1 - Decristoforo, Clemens T1 - Highlights lecture EANM 2015: the search for nuclear medicine's superheroes JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1). KW - Conjugate arc therapy KW - Phase-II KW - 18F-FDG PET/CT KW - Highlights Lecture KW - Molecular Imaging KW - Prostate-cancer KW - Radionuclide therapy KW - Myocardial perfusion KW - Preclinical evaluation KW - Targeted therapy KW - Thyroid cancer KW - SPECT KW - 2015 KW - EANM KW - Hamburg KW - Physics and instrumentation KW - Radiopharmacy KW - Oncology KW - Radionuclide Therapy KW - Cardiology KW - Neurosciences Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187613 VL - 43 IS - 10 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Wakabayashi, Hiroshi A1 - Chen, Xinyu A1 - Hayakawa, Nobuyuki A1 - Lapa, Constantin A1 - Rowe, Steven P. A1 - Javadi, Mehrbod S. A1 - Robinson, Simon A1 - Higuchi, Takahiro T1 - Ventricular distribution pattern of the novel sympathetic nerve PET radiotracer \(^{18}\)F-LMI1195 in Rabbit Hearts JF - Scientific Reports N2 - We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer \(^{18}\)F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of \(^{18}\)F-LMI1195. In healthy rabbits, \(^{18}\)F-LMI1195 was administered followed by the reference perfusion marker \(^{201}\)Tl for a dual-radiotracer analysis. After 20 min of \(^{18}\)F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-μm short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine \(^{18}\)F-LMI1195 distribution (exposure for 3 h). After complete \(^{18}\)F decay, sections were re-exposed to determine 201Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. \(^{18}\)F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 ± 2, 94 ± 5, 94 ± 4 and 97 ± 3%LV, respectively, n.s.). Subepicardial \(^{201}\)Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90 ± 3, 96 ± 2 and *80 ± 5%LV, respectively, *p < 0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of \(^{18}\)F-LMI1195 (90 ± 4, 96 ± 5 and 84 ± 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of \(^{201}\)Tl in comparison to \(^{18}\)F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts. KW - Cardiovascular diseases KW - Heart failure Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202707 VL - 9 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Derlin, Thorsten A1 - Lapa, Constantin A1 - Sheikbahaei, Sara A1 - Higuchi, Takahiro A1 - Giesel, Frederik L. A1 - Behr, Spencer A1 - Drzezga, Alexander A1 - Kimura, Hiroyuki A1 - Buck, Andreas K. A1 - Bengel, Frank M. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Rowe, Steven P. T1 - \(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging JF - Theranostics N2 - Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios. KW - Radiofluorine KW - prostate-specific membrane antigen KW - prostate cancer KW - \(^{18}\)F KW - PSMA KW - \(^{68}\)Ga KW - theranostics KW - radioligand therapy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202559 SN - 1838-7640 VL - 10 IS - 1 ER - TY - JOUR A1 - Breun, Maria A1 - Monoranu, Camelia M. A1 - Kessler, Almuth F. A1 - Matthies, Cordula A1 - Löhr, Mario A1 - Hagemann, Carsten A1 - Schirbel, Andreas A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Buck, Andreas K. A1 - Wester, Hans-Jürgen A1 - Ernestus, Ralf-Ingo A1 - Lapa, Constantin T1 - [\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas JF - Frontiers in Oncology N2 - We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression. KW - vestibular schwannoma KW - CXCR4 KW - PET/CT KW - molecular imaging KW - Pentixafor Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201863 VL - 9 IS - 503 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Kircher, Stefan A1 - Higuchi, Takahiro A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Wester, Hans-Jürgen A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Lapa, Constantin T1 - CXCR4-directed imaging in solid tumors JF - Frontiers in Oncology N2 - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT. Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients. KW - CXCR4 KW - [68Ga]Pentixafor KW - theranostics KW - solid tumors KW - chemokine receptor Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195678 SN - 2234-943X VL - 9 IS - 770 ER - TY - THES A1 - Soares Machado, Jéssica T1 - Dosimetry-based Assessment of Radiation-associated Cancer risk for \(^9\)\(^9\)\(^m\)Tc-MAG3 Scans in Infants and Optimization of Administered Activities for \(^6\)\(^8\)Ga-labelled Peptides in Children and Adolescents T1 - Dosimetrie-basierte Abschätzung des strahlungsassoziierten Krebsrisikos für \(^9\)\(^9\)\(^m\)Tc-MAG3-Scans bei Säuglingen und Optimierung der verabreichten Aktivitäten für \(^6\)\(^8\)Ga-markierte Peptide bei Kindern und Jugendlichen N2 - In 2006, 0.18 Mio pediatric nuclear medicine diagnostic exams were performed worldwide. However, for most of the radiopharmaceuticals used data on biokinetics and, as a consequence on dosimetry, are missing or have not been made publicly available. Therefore, most of the dosimetry assessments presented today for diagnostic agents in children and adolescents rely on the biokinetics data of adults. Even for one of the most common nuclear medicine exams for this patient group, renal scintigraphy with 99mTc-MAG3 for assessing renal function measured data on biokinetics is available only from a study performed on four children of different ages. In particular, renal scans are among the most frequent exams performed on infants and toddlers. Due to the young age, this patient group can be classified as a risk group with a higher probability of developing stochastic radiation effects compared to adults. As there are only limited data on biokinetics and dosimetry in this patient group, the aim of this study is to reassess the dosimetry and the associated radiation risk for a larger number of infants undergoing 99mTc-MAG3 renal scans based on a retrospective analysis of existing patient data. Data were collected retrospectively from 34 patients younger than 20 months with normal (20 patients) and abnormal renal function (14 patients) undergoing 99mTc-MAG3 scans. The patient-specific organ activity was estimated based on a retrospective calibration which was performed based on a set of two 3D-printed infant kidneys (newborns: 8.6 ml; 1-year-old: 23.4 ml) filled with known activities. Both phantoms were scanned at different positions along the anteroposterior axis inside a water phantom, providing depth- and size-dependent attenuation correction factors for planar imaging. Time-activity curves were determined by drawing kidney, bladder, and whole body regions-of-interest for each patient, and subsequently applying the calibration factor for conversion of counts to activity. Patient-specific time-integrated activity coefficients were obtained by integrating the organ-specific time-activity curves. Absorbed and effective dose coefficients for each patient were assessed with OLINDA/EXM for the provided newborn and 1-year-old phantom. Based on absorbed dose values, the radiation risk estimation was performed individually for each of the 34 patients with the National Cancer Institute’s Radiation Risk Assessment Tool. The patients’ organ-specific mean absorbed dose coefficients for the patients with normal renal function were 0.04±0.03 mGy/MBq for the kidneys and 0.27±0.24 mGy/MBq for the bladder. This resulted in a mean effective dose coefficient of 0.02±0.02 mSv/MBq. Based on the dosimetry results, the evaluation of the excess lifetime risk (ELR) for the development of radiation-induced cancer showed that the group of newborns has an ELR of 16.8 per 100,000 persons, which is higher in comparison with the 1-year-old group with an ELR of 14.7 per 100,000 persons. With regard to the 14 patients with abnormal renal function, the mean values for the organ absorbed dose coefficients for the patients were: 0.40±0.34 mGy/MBq for the kidneys and 0.46±0.37 mGy/MBq for the bladder. The corresponding effective dose coefficients (mSv/MBq) was: 0.05±0.02 mSv/MBq. The mean ELR (per 100,000 persons) for developing cancer from radiation exposure for patients with abnormal renal function was 29.2±18.7 per 100,000 persons. As a result, the radiation-associated stochastic risk increases with the organ doses, taking age- and gender-specific influences into account. Overall, the lifetime radiation risk associated with the 99mTc-MAG3 scans is very low in comparison to the general population risk for developing cancer. Furthermore, due to the increasing demand for PET-scans in children and adolescents with 68Ga-labelled peptides, in this work published data sets for those compounds were analyzed to derive recommendations for the administered activities in children and adolescents. The recommendation for the activities to be administered were based on the weight-independent effective dose model, proposed by the EANM Pediatric Dosage Card for application in pediatric nuclear medicine. The aim was to derive recommendations on administered activities for obtaining age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card, to determine the radiopharmaceutical class of 68Ga-labeled peptides (“multiples”), and to calculate the baseline activities based on the biokinetics of these compounds and an upper limit of the administered activity of 185 MBq for an adult. Analogous to 18F-fluoride, a minimum activity of 14 MBq is recommended. As a result, for those pediatric nuclear medicine applications involving 68Ga-labeled peptides, new values for the EANM dosage card were proposed and implemented based on the results derived in this work. Overall, despite the low additional radiation-related cancer risk, all efforts should be undertaken to optimize administered activities in children and adolescents for obtaining sufficient diagnostic information with minimal associated radiation risk. N2 - Im Jahr 2006 wurden weltweit 0,18 Mio. nuklearmedizinische Diagnostikuntersuchungen bei Kindern durchgeführt. Für die meisten Radiopharmazeutika fehlen jedoch Daten zur Biokinetik und damit zur Dosimetrie oder diese wurden nicht öffentlich zugänglich gemacht. Daher basieren die meisten der heute vorgestellten Dosimetriedaten für Diagnostika bei Kindern und Jugendlichen auf den biokinetischen Daten von Erwachsenen. Selbst für eine der häufigsten nuklearmedizinischen Untersuchungen für diese Patientengruppe, die Nierenszintigraphie mit 99mTc-MAG3 für Bestimmung der Nierenfunktion, wurden Daten zur Biokinetik bisher nur für vier Kinder unterschiedlichen Alters erhoben. Insbesondere Nierenuntersuchungen gehören zu den häufigsten Untersuchungen bei Säuglingen und Kleinkindern. Aufgrund des jungen Alters kann diese Patientengruppe als Hochrisikogruppe mit einer höheren Wahrscheinlichkeit für das Eintreten stochastischer Strahlenwirkungen im Vergleich zu Erwachsenen eingestuft werden. Da es in dieser Patientengruppe nur begrenzte Daten zur Biokinetik und Dosimetrie gibt, ist das Ziel dieser Arbeit, die Dosimetrie und das damit verbundene Strahlenrisiko für eine größere Anzahl von Kleinkindern, die sich 99mTc-MAG3-Nierenscans unterziehen, auf der Grundlage einer retrospektiven Analyse bestehender Patientendaten neu zu bewerten. Die Daten wurden retrospektiv von 34 Patienten unter 20 Monaten mit normaler (20 Patienten) und eingeschränkter Nierenfunktion (14 Patienten) erhoben, bei denen 99mTc-MAG3-Scans durchgeführt wurden. Die patientenspezifische Organaktivität wurde basierend auf einer retrospektiven Kalibrierung abgeschätzt. Diese Kalibrierung basiert auf einem Satz von zwei 3D-gedruckten Säuglingsnieren, die mit bekannten Aktivitäten gefüllt wurden. Beide Phantome wurden an verschiedenen Positionen entlang der anteroposterioren Achse innerhalb eines Wasserphantoms gescannt und lieferten tiefen- und größenabhängige Schwächungskorrekturfaktoren für die planare Bildgebung. Die Zeit-Aktivitäts-Kurven wurden bestimmt, indem für jeden Patienten Nieren-, Blasen- und Ganzkörperregionen eingezeichnet und anschließend der entsprechende Kalibrierfaktor für die Umwandlung der Zählraten in Aktivität angewendet wurde. Patientenspezifische zeitintegrierte Aktivitätskoeffizienten wurden durch Integration der organspezifischen Zeit-Aktivitätskurven ermittelt. Die Energie- und effektiven Dosiskoeffizienten für jeden Patienten wurden mit OLINDA/EXM für das bereitgestellte Neugeborenen- und 1-Jahres-Phantom ermittelt. Basierend auf diesen Werten für die Energiedosen wurde eine individuelle Abschätzung des Strahlenrisikos für jeden der 34 Patienten mit dem Radiation Risk Assessment Tool des National Cancer Institute durchgeführt. Die organspezifischen mittleren Energiedosiskoeffizienten der Patienten mit normaler Nierenfunktion lagen bei 0,04±0,03 mGy/MBq für die Nieren und 0,27±0,24 mGy/MBq für die Blase, was in einem mittleren effektiven Dosiskoeffizienten von 0,02±0,02 mSv/MBq resultiert. Basierend auf den Ergebnissen der Dosimetrie, zeigte die Auswertung des zusätzlichen Lebenszeitrisikos ("excess lifetime risk", ELR) für die Entwicklung von strahleninduziertem Krebs, dass die Gruppe der Neugeborenen ein ELR von 16,8 pro 100.000 Personen aufweist, was höher ist als das der Gruppe der 1-jährigen mit 14,7 pro 100.000 Personen. Bei den 14 Patienten mit abnormaler Nierenfunktion waren die Mittelwerte für die Koeffizienten der organspezifischen Energiedosen für die Patienten: 0,40±0,34 mGy/MBq für die Nieren; 0,46±0,37 mGy/MBq für die Blase. Der effektivendosiskoeffizienten (mSv/MBq) waren: 0,05±0,02 mSv/MBq. Der mittlere ELR (pro 100.000 Personen) für die Entstehung von Krebs durch die Strahlenexposition von Patienten mit abnormaler Nierenfunktion betrug 29,2±18,7 pro 100.000 Personen. Das mit der Strahlung verbundene stochastische Risiko steigt mit den Organdosen unter Berücksichtigung alters- und geschlechtsspezifischer Einflüsse. Im Allgemeinen ist das mit den 99mTc-MAG3-Scans verbundene lebenslange Strahlenrisiko im Vergleich zum allgemeinen Bevölkerungsrisiko für die Entstehung von Krebs sehr gering. Aufgrund der steigenden Nachfrage nach PET-Scans bei Kindern und Jugendlichen mit 68Ga-markierten Peptiden wurden zusätzlich publizierte Datensätze für diese Verbindungen analysiert, um Empfehlungen für zu verabreichende Aktivitäten bei Kindern und Jugendlichen abzuleiten. Die Dosisberechnungen dazu basierten auf dem Modell einer gewichtsunabhängigen effektiven Dosis, das von der EANM Pediatric Dosage Card für den Einsatz in der pädiatrischen Nuklearmedizin vorgeschlagen wurde. Ziel war es, Empfehlungen zu verabreichenden Aktivitäten so aufzuteilen, dass sich altersunabhängige effektive Dosen ergeben. Dazu wurden die entsprechenden gewichtsabhängigen effektiven Dosiskoeffizienten gemäß dem Formalismus der EANM-Dosierungsempfehlung neu berechnet, um die radiopharmazeutische Klasse der 68Ga-markierten Peptide ("Multiples") zu bestimmen und die Werte für Basisaktivität zu berechnen. Diese basierend auf den Biokinetiken dieser Verbindungen und einer Obergrenze der verabreichten Aktivität von 185 MBq für einen Erwachsenen. Analog zu 18F-Fluorid, wird eine Mindestaktivität von 14 MBq empfohlen. Darauf basierend wurden für die pädiatrischen nuklearmedizinischen Anwendungen mit 68Ga-markierten Peptiden neue Werte für die EANM-Dosierungsempfehlung vorgeschlagen. Insgesamt sollten, trotz des geringen zusätzlichen strahlenbedingten Krebsrisikos, alle Anstrengungen unternommen werden, um die verabreichten Aktivitäten bei Kindern und Jugendlichen zu optimieren, um ausreichende diagnostische Informationen bei minimalem zusätzlichem Strahlenrisiko zu erhalten. KW - Biokinetics KW - Absorbed Doses KW - Risk Assessment KW - Pediatric Patients KW - Dosimetry KW - Nuclear Medicine KW - Pediatric Nuclear Medicine KW - Diagnostic Imaging Exams KW - Radiation Protection KW - Administered Activities KW - Radiation-associated Cancer Risk KW - Ga-68-labelled Peptides KW - Tc-99m-MAG3 Scans Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192640 ER - TY - INPR A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. A1 - Bundschuh, Lena A1 - Javadi, Mehrbod S. A1 - Leal, Jeffrey P. A1 - Higuchi, Takahiro A1 - Pienta, Kenneth J. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging T2 - Journal of Nuclear Medicine N2 - Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center. Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed. Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005). Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials. KW - 18F-DCFPyL KW - Positronen-Emissions-Tomografie KW - PSMA-RADS KW - interreader KW - interobserver KW - PSMA KW - prostate cancer KW - RADS KW - reporting and data system KW - PET Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167788 SN - 0161-5505 N1 - This research was originally published in JNM. Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Mehrbod S. Javadi, Jeffrey P. Leal, Takahiro Higuchi, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Constantin Lapa and Steven P. Rowe. Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on 18F-DCFPyL PET/CT Imaging. J Nucl Med 2018;59:1857-1864 © SNMMI. ER - TY - JOUR A1 - Brumberg, Joachim A1 - Küsters, Sebastian A1 - Al-Momani, Ehab A1 - Marotta, Giorgio A1 - Cosgrove, Kelly P. A1 - van Dyck, Christopher H. A1 - Herrmann, Ken A1 - Homola, György A. A1 - Pezzoli, Gianni A1 - Buck, Andreas K. A1 - Volkmann, Jens A1 - Samnick, Samuel A1 - Isaias, Ioannis U. T1 - Cholinergic activity and levodopa-induced dyskinesia: a multitracer molecular imaging study JF - Annals of Clinical and Translational Neurology N2 - Objective: To investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease. Methods: This study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[\(^{123}\)I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [\(^{123}\)I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[\(^{18}\)F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed. Results: Density of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side. Interpretation: Our findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression. KW - levodopa-induced dyskinesia KW - cholinergic activity KW - Parkinson’s disease Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170406 VL - 4 IS - 9 ER - TY - JOUR A1 - Lapa, Constantin A1 - Kircher, Stefan A1 - Schirbel, Andreas A1 - Rosenwald, Andreas A1 - Kropf, Saskia A1 - Pelzer, Theo A1 - Walles, Thorsten A1 - Buck, Andreas K. A1 - Weber, Wolfgang A. A1 - Wester, Hans-Juergen A1 - Herrmann, Ken A1 - Lückerath, Katharina T1 - Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma? JF - Oncotarget N2 - C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy. KW - PET KW - CXCR4 KW - [\(^{68}\)Ga] pentixafor KW - pleural mesothelioma KW - theranostics Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169989 VL - 8 IS - 57 ER - TY - JOUR A1 - Lapa, Constantin A1 - Lückerath, Katharina A1 - Kleinlein, Irene A1 - Monoranu, Camelia Maria A1 - Linsenmann, Thomas A1 - Kessler, Almuth F. A1 - Rudelius, Martina A1 - Kropf, Saskia A1 - Buck, Andreas K. A1 - Ernestus, Ralf-Ingo A1 - Wester, Hans-Jürgen A1 - Löhr, Mario A1 - Herrmann, Ken T1 - \(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma JF - Theranostics N2 - Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. \(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy. KW - imaging KW - chemokine receptor-4 KW - glioblastoma KW - positron emission tomography/computed tomography KW - \(^{68}\)Ga-Pentixafor Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168174 VL - 6 IS - 3 ER - TY - THES A1 - Brumberg [geb. Ichouh], Dalma T1 - \(^{11}\)C-MET und \(^{18}\)F-FDG: \(In\) \(vitro\) Vergleich zur Bildgebung beim Multiplen Myelom im Kontext biologischer Charakteristika T1 - Imaging multiple myeloma with \(^{11}\)C-MET and \(^{18}\)F-FDG: \(In\) \(vitro\) comparison in the context of biological characteristics N2 - Das Multiple Myelom ist eine hämatologische Erkrankung, die durch die Proliferation von Plasmazellen und die Produktion von Antikörpern oder deren Leichtketten gekennzeichnet ist. Eine frühe Diagnosestellung durch Detektion sowohl intra- als auch extramedullärer Manifestationen ist für die Einleitung einer effektiven Therapie von entscheidender Bedeutung. Ebenso bedeutsam ist ein wirksames Therapiemonitoring. Wichtige diagnostische Modalitäten sind bei beiden Fragestellungen tomografische, bildgebende Verfahren. Hierbei wurde die Effektivität der 18F-FDG-PET/CT im Rahmen der Diagnose, des Stagings und der Prognoseabschätzung bereits nachgewiesen. Dennoch ist ihr klinischer Nutzen durch die geringe Sensitivität bei Detektion von diffusem Knochenmarksbefall und Vorliegen sowohl falsch positiver als auch falsch negativer Befunde limitiert. Die vorliegende Arbeit hat untersucht, ob der aminosäurebasierte Tracer 11C-MET über spezifische Eigenschaften verfügt, die eine höhere Sensitivität und Spezifität in der Detektion von Myelomzellen ermöglichen und ob der Radioligand dem etablierten Glukoseanalogon 18F-FDG überlegen ist. Hierfür wurden drei etablierte humane Myelomzelllinien, sowohl nativ als auch nach 48-stündiger Therapie mit dem Proteasominhibitor Carfilzomib, mit 18F-FDG und 11C-MET inkubiert und mithilfe eines Gammastrahlungszählers beurteilt. Zudem wurde untersucht, ob die Traceraufnahme mit spezifischen Charakteristika der Tumorbiologie korreliert. So wurde die Oberflächenexpression von CD138 und CXCR4, die intrazelluläre Expression der Leichtketten κ/λ und die Proliferation der Zelllinien mittels Durchflusszytometrie vor und nach Behandlung mit Carfilzomib eruiert. Die unbehandelten Zellen zeigten, verglichen zu 18F-FDG, bereits nach kürzester Inkubationsdauer eine 3-3,5-fach höhere 11C-MET Retention. Weiterhin zeigte sich die 11C-MET-Aufnahme nach Behandlung aller Zellreihen insgesamt marginal höher als die 18F-FDG-Aufnahme, während die Reduktion der 11C-MET-Anreicherung im prä- zu posttherapeutischen Vergleich für alle drei Zelllinien signifikant war. Eine mögliche Erklärung für diese Beobachtungen liefert die Myelombiologie: eine erhöhte Aufnahme der radioaktiv markierten Aminosäure durch MM-Zellen könnte durch eine Zunahme der Zellproliferation und insbesondere durch eine Steigerung der Proteinsynthese im Rahmen der überschießenden Produktion von M-Protein bedingt sein. In Zusammenschau könnte 11C-MET mit höherer Sensitivität Myelommanifestationen detektieren, wodurch ggf. Läsionen mit geringem Metabolismus dargestellt und eine bessere Beurteilung des Krankheitspogresses erfolgen könnte. Zudem bietet für den klinischen Einsatz die – verglichen zu 18F-FDG – größere Differenz der 11C-MET-Retention zwischen prä- und posttherapeutischer Messung die Möglichkeit einer besseren Beurteilbarkeit des Therapieansprechens. 11C-MET birgt ggf. das Potential auch minimale aktive Restherde zu detektieren und damit Patienten einem individualisierten Therapiekonzept zuzuführen. Ein Zusammenhang zwischen den untersuchten Biomarkern und der 11C-MET Retention bzw. deren Abnahme nach Behandlung konnte nicht gezeigt werden. Somit sollten für 11C-MET andere Biomarker herangezogen werden, um diese mit der Bildgebung zu korrelieren und zu bewerten. N2 - Multiple myeloma is a heterogeneous lymphoproliferative disease, which is characterized by an uncontrolled proliferation of clonal plasma cells. It is both essential to diagnose the disease at an early stage in order to prevent organ damage and to monitor therapy to adjust and individualize it. Imaging modalities like 18F-FDG-PET/CT play an important role for these purposes. However, its clinical benefit is limited due to the low detection rate of diffuse bone marrow invasion and false positive or negative findings. To overcome these limitations, we analysed if the amino acid-based tracer 11C-MET has specific features to reach a higher sensitivity and specificity in detecting myeloma cells. Therefore, three established human myeloma cell lines were incubated with 18F-FDG and 11C-MET natively without and after therapy with the proteasome inhibitor Carfilzomib and evaluated via gamma counter. The results showed a higher 11C-MET-uptake in untreated cells after a short time, a higher uptake after treatment with Carfilzomib and a significant reduction pre- to post therapy compared to 18F-FDG. These results assume that 11C-MET has the potential to be more sensitive in detecting myeloma manifestations as well as for the monitoring of disease activity during and after treatment. Furthermore, it might also have the potential to visualize minimal residual disease after treatment. This could lead to an early adaption of therapy and thereby may extend progression free survival. This study also investigated the relationship between specific biological characteristics of multiple myeloma (surface expression of CD138 and CXCR4, intracellular light chain production and proliferation rate) and radioligand uptake. A correlation between the markers and the uptake could not be proven, so that we assume that other biomarkers should be considered and correlated with 11C-MET to reflect tumor biology and verify possible prognostic markers. KW - Multiples Myelom KW - 11C-Methionin KW - Positronenemissionstomographie KW - 18F-FDG KW - CD138 KW - CXCR4 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181843 ER - TY - INPR A1 - Yin, Yafu A1 - Werner, Rudolf A. A1 - Higuchi, Takahiro A1 - Lapa, Constantin A1 - Pienta, Kenneth J. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Rowe, Steven P. T1 - Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMARADS- 3B Categories T2 - Journal of Nuclear Medicine N2 - Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa. Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy. Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up. Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy. KW - PSMA-RADS-3B KW - Positronen-Emissions-Tomografie KW - prostate-specific membrane antigen KW - prostate cancer KW - PSMA-targeted PET KW - PSMA-RADS-3A Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167594 SN - 0161-5505 N1 - This research was originally published in JNM. Yafu Yin, Rudolf A. Werner, Takahiro Higuchi, Constantin Lapa, Kenneth J. Pienta, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe. Follow-Up of Lesions with Equivocal Radiotracer Uptake on PSMA-Targeted PET in Patients with Prostate Cancer: Predictive Values of the PSMA-RADS-3A and PSMA-RADS-3B Categories. J Nucl Med. 2019;60:511-516 © SNMMI. ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Ordonez, Alvaro A. A1 - Sanchez-Bautista, Julian A1 - Marcus, Charles A1 - Lapa, Constantin A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Leal, Jeffrey P. A1 - Lodge, Martin A. A1 - Javadi, Mehrbod S. A1 - Jain, Sanjay K. A1 - Higuchi, Takahiro T1 - Novel functional renal PET imaging with 18F-FDS in human subjects JF - Clinical Nuclear Medicine N2 - The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure. KW - 2-deoxy-2-18F-fluoro-D-sorbitol KW - Positronen-Emissions-Tomografie KW - 18F-FDS KW - renal imaging KW - Positron-Emission Tomography KW - split renal function KW - kidney Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174634 SN - 0363-9762 VL - 44 IS - 5 ER - TY - THES A1 - Kajdi, Georg Wilhelm T1 - iROLL - 3D-bildnavigierte, radioaktivitätsgestützte Resektion des nicht-palpablen Mammakarzinoms T1 - iROLL - image-radioguided occult lesion localization in breast cancer N2 - In dieser prospektiven Studie wurde die Durchführbarkeit der 3D-bildnavigierten, radioaktivitätsgestützten Resektion des nicht-palpablen Mammakarzinoms (iROLL) unter Verwendung der freehand SPECT (fhSPECT)-Technologie untersucht. Das Verfahren wurde mit der als Goldstandard etablierten, drahtgestützten Lokalisation (WGL) verglichen. Sekundäre Endpunkte der Studie waren die erfolgreiche Sentinellymphknotenbiopsie (SLNB) mittels fhSPECT, der Patientenkomfort beider Verfahren, die mögliche Vorhersage tumorpositiver Resektatränder mittels fhSPECT, inklusive notwendiger Nachresektionen und der Einfluss von iROLL auf die OP-Dauer. Die fhSPECT-gestützte iROLL ist ein schmerzarmes, patientenfreundliches, zeiteffizientes und v.a. gut durchführbares brusterhaltendes Therapieverfahren (BET) ist. Gegenüber der WGL wird eine einzeitige Markierung zur Primarius- und SLN-Markierung möglich, ohne dabei auf eine visuell fassbare, intraoperative Navigationshilfe verzichten zu müssen. N2 - In this prospective pilot study the feasability of iROLL (image-radioguided occult lesion localization in breast cancer)was investigated and compared to the gold standard of wire-guided localization (WGL). Secondary end-points were the sucessfull sentinel lymph node biopsy (SLNB) with the fhSPECT technology, evaluation of patient comfort and the possible prediction of tumor-positive resection margins with fhSPECT. Additional resections due to positive fhSPECT-scans and influence an operation time were also evaluated. fhSPECT-guided iROLL is a less painful, patient-friendly, time efficient and easily feasible therapy regimen for breast conserving surgery (BET). Compared to WGL it enables a one-time tracer-application for tumor and SLN detection while maintaining a visual component for intraoperative navigation. KW - Brustkrebs KW - Lymphknoten KW - Gammaspektrometer KW - iROLL KW - fhSPECT KW - 3D-Bildnavigation KW - Mammakarzinom KW - SLNB Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180459 ER - TY - INPR A1 - Werner, Rudolf A. A1 - Bundschuh, Ralph A. A1 - Bundschuh, Lena A1 - Fanti, Stefano A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro A1 - Weich, A. A1 - Pienta, Kenneth J. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Gorin, Michael A. A1 - Herrmann, Ken A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - Novel Structured Reporting Systems for Theranostic Radiotracers T2 - Journal of Nuclear Medicine N2 - Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed. KW - standardized reporting KW - Positronen-Emissions-Tomografie KW - prostate cancer KW - neuroendocrine neoplasia KW - 68Ga-DOTATATE KW - 68Ga-DOTATOC KW - 68Ga-DOTANOC KW - somatostatin receptor KW - SSTR KW - prostate-specific membrane antigen KW - PSMA KW - RADS KW - PSMA-RADS KW - SSTR-RADS KW - MI-RADS KW - PROMISE Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174629 SN - 0161-5505 N1 - This research was originally published in JNM. Authors: Rudolf A. Werner, Ralph A. Bundschuh, Lena Bundschuh, Stefano Fanti, Mehrbod S. Javadi, Takahiro Higuchi, A. Weich, Kenneth J. Pienta, Andreas K. Buck, Martin G. Pomper, Michael A. Gorin, Ken Herrmann, Constantin Lapa, Steven P. Rowe. Novel Structured Reporting Systems for Theranostic Radiotracers. J Nucl Med May 1, 2019 vol. 60 no. 5 577-584 © SNMMI. ER - TY - JOUR A1 - Beykan, Seval A1 - Fani, Melpomeni A1 - Jensen, Svend Borup A1 - Nicolas, Guillaume A1 - Wild, Damian A1 - Kaufmann, Jens A1 - Lassmann, Michael T1 - In vivo biokinetics of \(^{177}\)Lu-OPS201 in Mice and Pigs as a Model for Predicting Human Dosimetry JF - Contrast Media & Molecular Imaging N2 - Introduction. \(^{177}\)Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of \(^{177}\)Lu-OPS201 in animals and humans. Methods. Data on biokinetics of \(^{177}\)Lu-OPS201 were analyzed in athymic nude Foxn1\(^{nu}\) mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19–0.27 MBq (mice), 97–113 MBq (pigs), and 850–1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results. A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs’ kidneys compared to the patient data (kidney TIAC: mice = 1.4 h, pigs = 7.7 h, and patients = 5.8 h; liver TIAC: mice = 0.7 h, pigs = 4.1 h, and patients = 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice = 3.9 h, pigs = 4.8 h, and patients = 5.8 h; liver TIAC: mice = 0.9 h, pigs = 4.7 h, and patients = 5.3 h). Conclusion. If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics. KW - medicine KW - neuroendocrine tumors KW - biokinetics KW - \(^{177}\)Lu-OPS201 KW - dosimetry Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177382 VL - 2019 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Marcus, Charles A1 - Sheikhbahaei, Sara A1 - Solnes, Lilja B. A1 - Leal, Jeffrey P. A1 - Du, Yong A1 - Rowe, Steven P. A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. T1 - Visual and Semiquantitative Accuracy in Clinical Baseline 123I-Ioflupane SPECT/CT Imaging JF - Clinical Nuclear Medicine N2 - PURPOSE: We aimed to (a) elucidate the concordance of visual assessment of an initial I-ioflupane scan by a human interpreter with comparison to results using a fully automatic semiquantitative method and (b) to assess the accuracy compared to follow-up (f/u) diagnosis established by movement disorder specialists. METHODS: An initial I-ioflupane scan was performed in 382 patients with clinically uncertain Parkinsonian syndrome. An experienced reader performed a visual evaluation of all scans independently. The findings of the visual read were compared with semiquantitative evaluation. In addition, available f/u clinical diagnosis (serving as a reference standard) was compared with results of the human read and the software. RESULTS: When comparing the semiquantitative method with the visual assessment, discordance could be found in 25 (6.5%) of 382 of the cases for the experienced reader (ĸ = 0.868). The human observer indicated region of interest misalignment as the main reason for discordance. With neurology f/u serving as reference, the results of the reader revealed a slightly higher accuracy rate (87.7%, ĸ = 0.75) compared to semiquantification (86.2%, ĸ = 0.719, P < 0.001, respectively). No significant difference in the diagnostic performance of the visual read versus software-based assessment was found. CONCLUSIONS: In comparison with a fully automatic semiquantitative method in I-ioflupane interpretation, human assessment obtained an almost perfect agreement rate. However, compared to clinical established diagnosis serving as a reference, visual read seemed to be slightly more accurate as a solely software-based quantitative assessment. KW - Single-Photon-Emissions-Computertomographie KW - SPECT KW - Parkinson’s disease KW - Parkinsonism KW - DaTscan KW - 123I-Ioflupane KW - SPECT KW - SPECT/CT Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168181 SN - 1536-0229 VL - 44 IS - 1 ER - TY - JOUR A1 - Eberlein, Uta A1 - Bröer, Jörn Hendrik A1 - Vandevoorde, Charlot A1 - Santos, Paula A1 - Bardiès, Manuel A1 - Bacher, Klaus A1 - Nosske, Dietmar A1 - Lassmann, Michael T1 - Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic nuclear medicine – a review JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.​peddose.​net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.​ncbi.​nlm.​nih.​gov/​pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained. KW - Dosimetry KW - Biokinetics KW - Diagnostic radiopharmaceuticals KW - Effective dose Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133846 VL - 38 IS - 12 ER - TY - THES A1 - Hartrampf, Philipp Emanuel T1 - Evaluation der PET-Tracer [\(^1\)\(^8\)F]FDG, [\(^1\)\(^8\)F]Cholin und [\(^6\)\(^8\)Ga]PSMA I&T zur nicht-invasiven Charakterisierung von Prostatakarzinomzellen und des Ansprechens auf eine Docetaxeltherapie T1 - Evaluation of PET tracers [\(^1\)\(^8\)F]FDG, [\(^1\)\(^8\)F]choline and [\(^6\)\(^8\)Ga]PSMA I&T for non-invasive characterization of prostate cancer cells and response to docetaxel therapy N2 - Das Prostatakarzinom (PCa) stellt derzeit in Deutschland die häufigste Krebserkrankung der männlichen Bevölkerung dar und steht bei den tödlich verlaufenden Malignomen an zweiter Stelle. Aktuell umfasst die Diagnostik immer öfter auch eine molekulare Bildgebung mittels PET/CT und den Tracern [18F]Cholin und [68Ga]PSMA. Letzterer detektiert selektiv das prostataspezifische Membranantigen (PSMA), welches in Prostatakarzinomzellen häufig überexprimiert ist. Das Wachstum von PCa geschieht in der Regel androgenabhängig, wobei sich auch teilweise eine androgenunabhängige Entwicklung findet. Für das bei kastrationsresistenten Karzinomen und fortgeschrittenen Stadien eingesetzte Chemotherapeutikum Docetaxel, werden immer wieder Resistenzentwicklungen beobachtet, wodurch dieses nur unzureichend effektiv ist. Ziel dieser Arbeit war es, die Eignung verschiedener PET-Tracer ([18F]FDG, [18F]Cholin und [68Ga]PSMA) zur Bildgebung androgenabhängiger und -unabhängiger Prostatakarzinomzellen zu testen sowie ihr Potential zur Beurteilung des Therapieansprechens auf Docetaxel zu untersuchen. Weiterhin sollte untersucht werden, ob die [68Ga]PSMA-Retention mit der PSMA-Expression korreliert. Im zweiten Teil wurde ein Zusammenhang zwischen der Expression von PSMA und der Resistenzentwicklung gegen Docetaxel untersucht. Methoden: Für die in-vitro Experimente wurden die hormonabhängige Zelllinie LNCaP sowie die hormonunabhängige Zelllinie LNCaP C4-2 verwendet. Im zweiten Teil wurden zusätzlich PSMA-negative PC-3 Zellen eingesetzt. Die aufgenommene bzw. gebundene Traceraktivität wurde mittels Gammacounter gemessen. Die Untersuchung der PSMA-Expression erfolgte mit Western-Blot und Durchflusszytometrie. Ein PSMA-Knockdown-System wurde mittels siRNA in LNCaP-Zellen etabliert. Ergebnisse: Die PSMA-Expression und die Sensitivität gegenüber Docetaxel waren bei LNCaP Zellen tendenziell erhöht gegenüber der LNCaP C4-2 Zelllinie. Nach Docetaxelbehandlung zeigte sich in beiden Zellreihen eine unveränderte PSMA-Expression. Der PSMA-spezifische PET-Tracer zeigte, im Vergleich zu den metabolischen Tracern [18F]FDG und [18F]Cholin, eine nur sehr geringe Retention. Im Vergleich der Zelllinien untereinander nahmen LNCaP C4-2 Zellen ca. 50 % mehr [18F]FDG auf als LNCaP Zellen. Die Aufnahme von [18F]Cholin unterschied sich nicht signifikant. Der Tracer [68Ga]PSMA zeigte eine höhere Bindung an LNCaP Zellen im Vergleich zu LNCaP C4-2 Zellen. In weiteren Versuchen konnte gezeigt werden, dass sowohl [18F]FDG als auch [18F]Cholin, nicht jedoch [68Ga]PSMA in vitro ein Therapieansprechen auf Docetaxel durch verminderte Traceraufnahme in beiden Zelllinien aufzeigen. Es konnte zudem eine direkte Korrelation zwischen der [68Ga]PSMA-Bindung und der PSMA-Expression nachgewiesen werden. Nach einer siRNA-vermittelten Verminderung der PSMA-Expression in LNCaP Zellen (Knockdown-Zellen) zeigte sich eine deutlich geringere Sensitivität für Docetaxel. Gleichzeitig war jedoch die Docetaxelsensitivität von PSMA-negativen PC-3 Zellen höher als die von LNCaP Knockdown-Zellen. Schlussfolgerung: Insgesamt zeigten unsere Untersuchungen, dass sich die PET-Tracer [18F]FDG und [68Ga]PSMA zur Unterscheidung des androgenabhängigen Zellmodells vom androgenunabhängigen Modell eignen. Außerdem ermöglicht der [68Ga]PSMA-Tracer eine Einschätzung der PSMA-Expression. Die Tracer [18F]FDG und [18F]Cholin eignen sich in vitro für die Beurteilung des Therapieansprechens einer Docetaxeltherapie, [68Ga]PSMA dagegen nicht. Die PSMA-Expression scheint ein entscheidender, aber nicht alleinstehender Faktor für die Sensitivität von LNCaP Zellen gegenüber Docetaxel zu sein. Es scheinen hierbei allerdings eher der Verlust von PSMA, wie im Knockdown-Modell induziert, sowie bislang unbekannte Faktoren eine wichtige Rolle zu spielen. N2 - Prostate carcinoma (PCa) is currently the most frequent cancer in men in Germany and is the second leading cause of cancer deaths. Currently, diagnostics more and more often include molecular imaging using PET/CT and the tracers [18F]choline and [68Ga]PSMA. The latter selectively detects the prostate-specific membrane antigen (PSMA), which is often overexpressed in prostate cancer cells. The growth of PCa is usually androgen-dependent, although it is sometimes also developing independently of androgen. For the chemotherapeutic agent docetaxel, which is used for castration-resistant carcinomas and advanced stages, the development of resistance is observed again and again, resulting in insufficient efficacy. The aim of this work was to evaluate the potential of different PET tracers ([18F]FDG, [18F]Choline and [68Ga]PSMA) for the imaging of androgen-dependent and independent prostate carcinoma cells as well as their potential for the assessment of therapy response to docetaxel. Furthermore, it should be investigated whether [68Ga]PSMA uptake correlates with PSMA expression. In the second part, an association between the expression of PSMA and the development of resistance to docetaxel was investigated. Methods: For the in vitro experiments the hormone-dependent cell line LNCaP and the hormone-independent cell line LNCaP C4-2 were used. In the second part PSMA-negative PC-3 cells were additionally used. The tracer uptake and binding activity was measured by gamma counter. PSMA expression was determined by Western blot and flow cytometry. A PSMA knockdown system was established in LNCaP cells using siRNA. Results: PSMA expression and sensitivity to docetaxel were increased in LNCaP cells compared to the LNCaP C4-2 cells. After docetaxel treatment, both cell lines showed unchanged PSMA expression. Compared to the metabolic tracers [18F]FDG and [18F]choline, the PSMA-specific PET tracer showed very low uptake. In comparison of the cell lines, LNCaP C4-2 cells took up about 50 % more [18F]FDG than LNCaP cells. The uptake of [18F]choline did not differ significantly. The tracer [68Ga]PSMA showed a higher binding to LNCaP cells compared to LNCaP C4-2 cells. In further experiments it was observed that both [18F]FDG and [18F]choline, but not [68Ga]PSMA, in vitro showed a therapy response to docetaxel by reduced tracer uptake in both cell lines. A direct correlation between [68Ga]PSMA binding and PSMA expression was also found. After a siRNA-mediated reduction of PSMA expression in LNCaP cells (knockdown cells), a significantly lower sensitivity for docetaxel was observed. At the same time, however, the docetaxel sensitivity of PSMA-negative PC-3 cells was higher than that of LNCaP knockdown cells. Conclusion: Overall, our investigations showed that the PET tracers [18F]FDG and [68Ga]PSMA are suitable for differentiating the androgen-dependent cell model from the androgen-independent model. In addition, the [68Ga]PSMA tracer allows an assessment of PSMA expression. The tracers [18F]FDG and [18F]choline are suitable for in vitro assessment of response to docetaxel therapy, whereas [68Ga]PSMA is not. PSMA expression seems to be a critical, but not unique, factor for the sensitivity of LNCaP cells to docetaxel. However, the loss of PSMA, as induced in the knockdown model, as well as unknown factors seem to play an important role. KW - Positronen-Emissions-Tomografie KW - PSMA KW - [18]F-Cholin KW - [68]Ga-PSMA I&T KW - Docetaxel KW - LNCaP KW - [18]F-choline Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176299 ER - TY - JOUR A1 - Schuhmann, Sarah A1 - Eberlein, Uta A1 - Müller, Jessica A1 - Scherthan, Harry A1 - Lassmann, Michael T1 - Correlation of the absorbed dose to the blood and DNA damage in leukocytes after internal ex-vivo irradiation of blood samples with Ra-224 JF - EJNMMI Research N2 - Background: Irradiation with α-particles creates densely packed damage tracks along particle trajectories in exposed cells, including complex DNA damage and closely spaced double-strand breaks (DSBs) in hit nuclei. Here, we investigated the correlation of the absorbed dose to the blood and the number of α-induced DNA damage tracks elicited in human blood leukocytes after ex-vivo in-solution exposure with Ra-224. The aim was to compare the data to previously published data on Ra-223 and to investigate differences in DNA damage induction between the two radium isotopes. Results: Blood samples from three healthy volunteers were exposed ex-vivo to six different concentrations of Ra-224 dichloride. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the Ra-224 decay chain, ranging from 0 to 127 mGy. γ-H2AX + 53BP1 DNA damage co-staining and analysis was performed on ethanol-fixed leukocytes isolated from the irradiated blood samples. For damage quantification, α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci were enumerated in the exposed leukocytes. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values. Conclusions: Our data provide a first estimation of the DNA damage induced by Ra-224 in peripheral blood mononuclear cells. A comparison with our previously published Ra-223 data suggests that there is no difference in the induction of radiation-induced DNA damage between the two radium isotopes due to their similar decay properties. KW - 53BP1 KW - DNA damage KW - γ-H2AX KW - biological dosimetry KW - absorbed dose to the blood KW - α-emitter KW - Ra-224 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176593 VL - 8 IS - 77 ER - TY - JOUR A1 - Schumann, Sarah A1 - Eberlein, Uta A1 - Muhtadi, Razan A1 - Lassmann, Michael A1 - Scherthan, Harry T1 - DNA damage in leukocytes after internal ex-vivo irradiation of blood with the α-emitter Ra-223 JF - Scientific Reports N2 - Irradiation with high linear energy transfer α-emitters, like the clinically used Ra-223 dichloride, severely damages cells and induces complex DNA damage including closely spaced double-strand breaks (DSBs). As the hematopoietic system is an organ-at-risk for the treatment, knowledge about Ra-223-induced DNA damage in blood leukocytes is highly desirable. Therefore, 36 blood samples from six healthy volunteers were exposed ex-vivo (in solution) to different concentrations of Ra-223. Absorbed doses to the blood were calculated assuming local energy deposition of all α- and β-particles of the decay, ranging from 0 to 142 mGy. γ-H2AX + 53BP1 co-staining and analysis was performed in leukocytes isolated from the irradiated blood samples. For DNA damage quantification, leukocyte samples were screened for occurrence of α-induced DNA damage tracks and small γ-H2AX + 53BP1 DSB foci. This revealed a linear relationship between the frequency of α-induced γ-H2AX damage tracks and the absorbed dose to the blood, while the frequency of small γ-H2AX + 53BP1 DSB foci indicative of β-irradiation was similar to baseline values, being in agreement with a negligible β-contribution (3.7%) to the total absorbed dose to the blood. Our calibration curve will contribute to the biodosimetry of Ra-223-treated patients and early after incorporation of α-emitters. KW - alpha particles KW - blood KW - DNA Breaks KW - double-stranded KW - gamma rays KW - healthy volunteers KW - humans KW - leukocytes KW - radiation effects KW - radium Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175596 VL - 8 IS - 2286 ER - TY - JOUR A1 - Soares Machado, J. A1 - Tran-Gia, J. A1 - Schlögl, S. A1 - Buck, A. K. A1 - Lassmann, M. T1 - Biokinetics, dosimetry, and radiation risk in infants after \(^{99m}\)Tc-MAG3 scans JF - EJNMMI Research N2 - Background: Renal scans are among the most frequent exams performed on infants and toddlers. Due to the young age, this patient group can be classified as a high-risk group with a higher probability for developing stochastic radiation effects compared to adults. As there are only limited data on biokinetics and dosimetry in this patient group, the aim of this study was to reassess the dosimetry and the associated radiation risk for infants undergoing \(^{99m}\)Tc-MAG3 renal scans based on a retrospective analysis of existing patient data. Consecutive data were collected from 20 patients younger than 20 months (14 males; 6 females) with normal renal function undergoing \(^{99m}\)Tc-MAG3 scans. To estimate the patient-specific organ activity, a retrospective calibration was performed based on a set of two 3D-printed infant kidneys filled with known activities. Both phantoms were scanned at different positions along the anteroposterior axis inside a water phantom, providing depth- and size-dependent attenuation correction factors for planar imaging. Time-activity curves were determined by drawing kidney, bladder, and whole-body regions-of-interest for each patient, and subsequently applying the calibration factor for conversion of counts to activity. Patient-specific time-integrated activity coefficients were obtained by integrating the organ-specific time-activity curves. Absorbed and effective dose coefficients for each patient were assessed with OLINDA/EXM for the provided newborn and 1-year-old model. The risk estimation was performed individually for each of the 20 patients with the NCI Radiation Risk Assessment Tool. Results: The mean age of the patients was 7.0 ± 4.5 months, with a weight between 5 and 12 kg and a body size between 60 and 89 cm. The injected activities ranged from 12 to 24 MBq of \(^{99m}\)Tc-MAG3. The patients' organ-specific mean absorbed dose coefficients were 0.04 ± 0.03 mGy/MBq for the kidneys and 0.27 ± 0.24 mGy/MBq for the bladder. The mean effective dose coefficient was 0.02 ± 0.02 mSv/MBq. Based on the dosimetry results, an evaluation of the excess lifetime risk for the development of radiation-induced cancer showed that the group of newborns has a risk of 16.8 per 100,000 persons, which is about 12% higher in comparison with the 1-year-old group with 14.7 per 100,000 persons (all values are given as mean plus/minus one standard deviation except otherwise specified). Conclusion: In this study, we retrospectively derived new data on biokinetics and dosimetry for infants with normal kidney function after undergoing renal scans with \(^{99m}\)Tc-MAG3. In addition, we analyzed the associated age- and gender-specific excess lifetime risk due to ionizing radiation. The radiation-associated stochastic risk increases with the organ doses, taking age- and gender-specific influences into account. Overall, the lifetime radiation risk associated with the \(^{99m}\)Tc-MAG3 scans is very low in comparison to the general population risk for developing cancer. KW - \(^{99m}\)Tc-MAG3 KW - absorbed dose KW - biokinetics KW - dosimetry KW - pediatric patients KW - risk assessment Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175582 VL - 8 IS - 10 ER - TY - JOUR A1 - Kazuhino, Koshino A1 - Werner, Rudolf A. A1 - Toriumi, Fuijo A1 - Javadi, Mehrbod S. A1 - Pomper, Martin G. A1 - Solnes, Lilja B. A1 - Verde, Franco A1 - Higuchi, Takahiro A1 - Rowe, Steven P. T1 - Generative Adversarial Networks for the Creation of Realistic Artificial Brain Magnetic Resonance Images JF - Tomography N2 - Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)-based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%-60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for "data-hungry" technologies, such as supervised machine learning approaches, in various clinical applications. KW - AI KW - Magnetresonanztomografie KW - artificial intelligence KW - magnetic resonance imaging KW - MRI KW - DCGAN KW - GAN KW - stroke KW - machine learning Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172185 VL - 4 IS - 4 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Weich, Alexander A1 - Kircher, Malte A1 - Solnes, Lilja B. A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Rowe, Steven A1 - Lapa, Constantin T1 - The theranostic promise for neuroendocrine tumors in the late 2010s – Where do we stand, where do we go? JF - Theranostics N2 - More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context. KW - theranostics KW - Positronen-Emissions-Tomografie KW - PRRT KW - somatostatin receptor KW - peptide receptor radionuclide therapy KW - neuroendocrine tumor Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170264 VL - 8 IS - 22 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Eissler, Christoph A1 - Hayakawa, Nobuyuki A1 - Arias-Loza, Paula A1 - Wakabayashi, Hiroshi A1 - Javadi, Mehrbod S. A1 - Chen, Xinyu A1 - Shinaji, Tetsuya A1 - Lapa, Constantin A1 - Pelzer, Theo A1 - Higuchi, Takahiro T1 - Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET JF - Scientific Reports N2 - In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent. KW - diabetic cardiomyopathy KW - personalized treatment KW - precision medicine KW - ZDF rats KW - ECG KW - PET KW - \(^{18}\)F-fluorodeoxyglucose KW - \(^{18}\)F-FDG KW - diabetes Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171765 VL - 8 IS - 17631 ER - TY - JOUR A1 - Chen, Xinyu A1 - Werner, Rudolf A. A1 - Javadi, Mehrbod S. A1 - Maya, Yoshifumi A1 - Decker, Michael A1 - Lapa, Constantin A1 - Herrmann, Ken A1 - Higuchi, Takahiro T1 - Radionuclide imaging of neurohormonal system of the heart JF - Theranostics N2 - Heart failure is one of the growing causes of death especially in developed countries due to longer life expectancy. Although many pharmacological and instrumental therapeutic approaches have been introduced for prevention and treatment of heart failure, there are still limitations and challenges. Nuclear cardiology has experienced rapid growth in the last few decades, in particular the application of single photon emission computed tomography (SPECT) and positron emission tomography (PET), which allow non-invasive functional assessment of cardiac condition including neurohormonal systems involved in heart failure; its application has dramatically improved the capacity for fundamental research and clinical diagnosis. In this article, we review the current status of applying radionuclide technology in non-invasive imaging of neurohormonal system in the heart, especially focusing on the tracers that are currently available. A short discussion about disadvantages and perspectives is also included. KW - SPECT KW - radiotracer KW - heart failure KW - cardiac neurohormonal system KW - nuclear cardiology KW - PET Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-149205 VL - 5 IS - 6 ER - TY - JOUR A1 - Philipp-Abbrederis, Kathrin A1 - Herrmann, Ken A1 - Knop, Stefan A1 - Schottelius, Margret A1 - Eiber, Matthias A1 - Lückerath, Katharina A1 - Pietschmann, Elke A1 - Habringer, Stefan A1 - Gerngroß, Carlos A1 - Franke, Katharina A1 - Rudelius, Martina A1 - Schirbel, Andreas A1 - Lapa, Constantin A1 - Schwamborn, Kristina A1 - Steidle, Sabine A1 - Hartmann, Elena A1 - Rosenwald, Andreas A1 - Kropf, Saskia A1 - Beer, Ambros J A1 - Peschel, Christian A1 - Einsele, Hermann A1 - Buck, Andreas K A1 - Schwaiger, Markus A1 - Götze, Katharina A1 - Wester, Hans-Jürgen A1 - Keller, Ulrich T1 - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma JF - EMBO Molecular Medicine N2 - CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases. KW - FDG PET/CT KW - cells KW - CXCR4/SDF-1 KW - CXCR4 KW - multiple myeloma KW - positron emission tomography KW - chemokine receptor KW - in vivo imaging KW - malignancies KW - involvement KW - microenvironment KW - survival KW - cancer KW - autologous transplantation KW - bone disease Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738 VL - 7 IS - 4 ER - TY - JOUR A1 - Eberlein, Uta A1 - Peper, Michel A1 - Fernández, Maria A1 - Lassmann, Michael A1 - Scherthan, Harry T1 - Calibration of the \(\gamma\)-H2AX DNA double strand break focus assay for internal radiation exposure of blood lymphocytes JF - PLoS ONE N2 - DNA double strand break (DSB) formation induced by ionizing radiation exposure is indicated by the DSB biomarkers \(\gamma\)-H2AX and 53BP1. Knowledge about DSB foci formation in-vitro after internal irradiation of whole blood samples with radionuclides in solution will help us to gain detailed insights about dose-response relationships in patients after molecular radiotherapy (MRT). Therefore, we studied the induction of radiation-induced co-localizing \(\gamma\)-H2AX and 53BP1 foci as surrogate markers for DSBs in-vitro, and correlated the obtained foci per cell values with the in-vitro absorbed doses to the blood for the two most frequently used radionuclides in MRT (I-131 and Lu-177). This approach led to an in-vitro calibration curve. Overall, 55 blood samples of three healthy volunteers were analyzed. For each experiment several vials containing a mixture of whole blood and radioactive solutions with different concentrations of isotonic NaCl-diluted radionuclides with known activities were prepared. Leukocytes were recovered by density centrifugation after incubation and constant blending for 1 h at 37°C. After ethanol fixation they were subjected to two-color immunofluorescence staining and the average frequencies of the co-localizing \(\gamma\)-H2AX and 53BP1 foci/nucleus were determined using a fluorescence microscope equipped with a red/green double band pass filter. The exact activity was determined in parallel in each blood sample by calibrated germanium detector measurements. The absorbed dose rates to the blood per nuclear disintegrations occurring in 1 ml of blood were calculated for both isotopes by a Monte Carlo simulation. The measured blood doses in our samples ranged from 6 to 95 mGy. A linear relationship was found between the number of DSB-marking foci/nucleus and the absorbed dose to the blood for both radionuclides studied. There were only minor nuclide-specific intra-and inter-subject deviations. KW - in vivo formation KW - chromatin mobility KW - phosphorylation KW - repair KW - 53BP1 KW - damage KW - radioiodine therapy KW - thyroid cancer KW - histone H2AX KW - dose response Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148697 VL - 10 IS - 4 ER - TY - JOUR A1 - Lückerath, Katharina A1 - Lapa, Constantin A1 - Albert, Christa A1 - Herrmann, Ken A1 - Jörg, Gerhard A1 - Samnick, Samuel A1 - Einsele, Herrmann A1 - Knop, Stefan A1 - Buck, Andreas K. T1 - \(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma JF - Oncotarget N2 - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future. KW - positron emission tomography KW - imaging techniques KW - experience KW - \(^{11}\)C-Methionine-PET KW - treatment response KW - molecular imaging KW - multiple myeloma KW - management KW - \(^{18}\)F-FDG PET/CT KW - bone disease KW - stem-cell transplantation KW - esophagogastric junction Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148688 VL - 6 IS - 10 ER - TY - JOUR A1 - Nose, Naoko A1 - Werner, Rudolf A. A1 - Ueda, Yuichiro A1 - Günther, Katharina A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. A1 - Fukushima, Kazuhito A1 - Edenhofer, Frank A1 - Higuchi, Takahiro T1 - Metabolic substrate shift in human induced pluripotent stem cells during cardiac differentiation: Functional assessment using in vitro radionuclide uptake assay JF - International Journal of Cardiology N2 - BACKGROUND: Recent developments in cellular reprogramming technology enable the production of virtually unlimited numbers of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Although hiPSC-CM share various characteristic hallmarks with endogenous cardiomyocytes, it remains a question as to what extent metabolic characteristics are equivalent to mature mammalian cardiomyocytes. Here we set out to functionally characterize the metabolic status of hiPSC-CM in vitro by employing a radionuclide tracer uptake assay. MATERIAL AND METHODS: Cardiac differentiation of hiPSC was induced using a combination of well-orchestrated extrinsic stimuli such as WNT activation (by CHIR99021) and BMP signalling followed by WNT inhibition and lactate based cardiomyocyte enrichment. For characterization of metabolic substrates, dual tracer uptake studies were performed with \(^{18}\)F‑2‑fluoro‑2‑deoxy‑d‑glucose (\(^{18}\)F-FDG) and \(^{125}\)I‑β‑methyl‑iodophenyl‑pentadecanoic acid (\(^{125}\)I-BMIPP) as transport markers of glucose and fatty acids, respectively. RESULTS: After cardiac differentiation of hiPSCs, in vitro tracer uptake assays confirmed metabolic substrate shift from glucose to fatty acids that was comparable to those observed in native isolated human cardiomyocytes. Immunostaining further confirmed expression of fatty acid transport and binding proteins on hiPSC-CM. CONCLUSIONS: During in vitro cardiac maturation, we observed a metabolic shift to fatty acids, which are known as a main energy source of mammalian hearts, suggesting hi-PSC-CM as a potential functional phenotype to investigate alteration of cardiac metabolism in cardiac diseases. Results also highlight the use of available clinical nuclear medicine tracers as functional assays in stem cell research for improved generation of autologous differentiated cells for numerous biomedical applications. KW - tracer KW - Stammzelle KW - induced pluripotent stem cells KW - cardiomyocytes KW - fatty acid KW - stem cell therapy KW - hiPSC-CM Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170699 VL - 269 ER - TY - JOUR A1 - Werner, Rudolf A1 - Hänscheid, Heribert A1 - Leal, Jeffrey P. A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro A1 - Lodge, Martin A. A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Lapa, Constantin A1 - Rowe, Steven P. T1 - Impact of Tumor Burden on Quantitative [\(^{68}\)Ga]DOTATOC Biodistribution JF - Molecular Imaging and Biology N2 - Purpose: As has been previously reported, the somatostatin receptor (SSTR) imaging agent [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotate ([\(^{68}\)Ga]DOTATATE) demonstrates lower uptake in normal organs in patients with a high neuroendocrine tumor (NET) burden. Given the higher SSTR affinity of [\(^{68}\)Ga]DOTATATE, we aimed to quantitatively investigate the biodistribution of [\(^{68}\)Ga]-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ([68Ga]DOTATOC) to determine a potential correlation between uptake in normal organs and NET burden. Procedures: Of the 44 included patients, 36/44 (82%) patients demonstrated suspicious radiotracer uptake on [\(^{68}\)Ga]DOTATOC positron emission tomography (PET)/x-ray computed tomography (CT). Volumes of Interest (VOIs) were defined for tumor lesions and normal organs (spleen, liver, kidneys, adrenals). Mean body weight corrected standardized uptake value (SUV\(_{mean}\)) for normal organs was assessed and was used to calculate the corresponding mean specific activity uptake (Upt: fraction of injected activity per kg of tissue). For the entire tumor burden, SUV\(_{mean}\), maximum standardized uptake value (SUV\(_{max}\)), and the total mass (TBM) was calculated and the decay corrected tumor fractional uptake (TBU) was assessed. A Spearman’s rank correlation coefficient was used to determine the correlations between normal organ uptake and tumor burden. Results: The median SUV\(_{mean}\) was 18.7 for the spleen (kidneys, 9.2; adrenals, 6.8; liver, 5.6). For tumor burden, the median values were SUV\(_{mean}\) 6.9, SUV\(_{max}\) 35.5, TBM 42.6g, and TBU 1.2%. With increasing volume of distribution, represented by lean body mass and body surface area (BSA), Upt decreased in kidneys, liver, and adrenal glands and SUV\(_{mean}\) increased in the spleen. Correlation improved only for both kidneys and adrenals when the influence of the tumor uptake on the activity available for organ uptake was taken into account by the factor 1/(1-TBU). TBU was neither predictive for SUV\(_{mean}\) nor for Upt in any of the organs. The distribution of organ Upt vs. BSA/(1-TBU) were not different for patients with minor TBU (<3%) vs. higher TBU (>7%), indicating that the correlations observed in the present study are explainable by the body size effect. High tumor mass and uptake mitigated against G1 NET. Conclusions: There is no significant impact on normal organ biodistribution with increasing tumor burden on [\(^{68}\)Ga]DOTATOC PET/CT. Potential implications include increased normal organ dose with [\(^{177}\)Lu-DOTA]\(^0\)-D-Phe\(^1\)-Tyr\(^3\)-Octreotide and decreased absolute lesion detection with [\(^{68}\)Ga]DOTATOC in high NET burden. KW - somatostatin receptor KW - Positronen-Emissions-Tomografie KW - quantification KW - [68Ga]DOTATOC KW - neuroendocrine tumor KW - SSTR-PET KW - theranostics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170280 ER - TY - JOUR A1 - Werner, R.A. A1 - Schmid, J.S. A1 - Muegge, D.O. A1 - Lückerath, K. A1 - Higuchi, T. A1 - Hänscheid, H. A1 - Grelle, I. A1 - Reiners, C. A1 - Herrmann, K. A1 - Buck, A.K. A1 - Lapa, C. T1 - Prognostic value of serum tumor markers in medullary thyroid cancer patients undergoing vandetanib treatment JF - Medicine N2 - Tyrosine kinase inhibitors (TKIs) such as vandetanib have shown clinical effectiveness in advanced medullary thyroid cancer (MTC). During TKI treatment, fluctuations in the tumor markers carcinoembryonic antigen (CEA) and calcitonin (CTN) are frequently observed. Their role for treatment monitoring and the decision-making process has not been fully elucidated yet. Twenty-one patients (male, 16, female, 5; mean age, 49±13 years) with progressive MTC receiving vandetanib (300mg orally per day) were considered. Tumor restaging was performed every 3 months including contrast-enhanced computed tomography (CT). Response was assessed according to recent criteria (Response Evaluation Criteria in Solid Tumors, RECIST 1.1). Additionally, CEA and CTN were measured at the day of CT imaging and alterations observed in tumor markers were compared to respective imaging findings (partial response, PR; stable disease, SD; progressive disease, PD). During long-term follow-up (510±350 days [range, 97-1140 days]), CTN and CEA levels initially dropped in 71.4% and 61.9% of the patients followed by fluctuations in serum marker levels. A rise in CTN ≥39.5% between 2 subsequent measurements (defined by ROC analysis) had a sensitivity of 70.6% and a specificity of 83.2% in predicting PD with an accuracy of 82.0% (area under the curve (AUC), 0.76). Oscillations in CEA levels were not predictive for PD. Whereas tumor marker fluctuations in MTC patients undergoing TKI treatment are a frequent phenomenon, a significant rise in CTN ≥40% turns out to as an early indicator of tumor progression. KW - follow-up KW - kinase inhibitor KW - carcinoma KW - calcitonin KW - trial KW - medullary thyroid cancer Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145154 VL - 94 IS - 45 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Chen, Xinyu A1 - Rowe, Steven P. A1 - Lapa, Constantin A1 - Javadi, Mehrbod S. A1 - Higuchi, Takahiro T1 - Moving into the Next Era of PET Myocardial Perfusion Imaging - Introduction of Novel \(^{18}\)F-labeled Tracers JF - The International Journal of Cardiovascular Imaging N2 - The heart failure (HF) epidemic continues to rise with coronary artery disease (CAD) as one of its main causes. Novel concepts for risk stratification to guide the referring cardiologist towards revascularization procedures are of significant value. Myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) agents has demonstrated high accuracy for the detection of clinically relevant stenoses. With positron emission tomography (PET) becoming more widely available, mainly due to its diagnostic performance in oncology, perfusion imaging with that modality is more practical than in the past and overcomes existing limitations of SPECT MPI. Advantages of PET include more reliable quantification of absolute myocardial blood flow, the routine use of computed tomography for attenuation correction, a higher spatiotemporal resolution and a higher count sensitivity. Current PET radiotracers such as rubidium-82 (half-life, 76 sec), oxygen-15 water (2 min) or nitrogen-13 ammonia (10 min) are labeled with radionuclides with very short half-lives, necessitating that stress imaging is performed under pharmacological vasodilator stress instead of exercise testing. However, with the introduction of novel 18F-labeled MPI PET radiotracers (half-life, 110 min), the intrinsic advantages of PET can be combined with exercise testing. Additional advantages of those radiotracers include, but are not limited to: potentially improved cost-effectiveness due to the use of pre-existing delivery systems and superior imaging qualities, mainly due to the shortest positron range among available PET MPI probes. In the present review, widely used PET MPI radiotracers will be reviewed and potential novel 18F-labeled perfusion radiotracers will be discussed. KW - heart failure with mid-range ejection fraction KW - Positronenemissionstomografie KW - coronary artery disease KW - precision medicine KW - positron emission tomography KW - PET KW - SPECT KW - myocardial perfusion imaging KW - MPI KW - 18F-flurpiridaz KW - 18FFBnTP KW - HFmrEF Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169134 SN - 1569-5794 ER -