TY - JOUR
A1 - Marquardt, André
A1 - Hartrampf, Philipp
A1 - Kollmannsberger, Philip
A1 - Solimando, Antonio G.
A1 - Meierjohann, Svenja
A1 - Kübler, Hubert
A1 - Bargou, Ralf
A1 - Schilling, Bastian
A1 - Serfling, Sebastian E.
A1 - Buck, Andreas
A1 - Werner, Rudolf A.
A1 - Lapa, Constantin
A1 - Krebs, Markus
T1 - Predicting microenvironment in CXCR4- and FAP-positive solid tumors — a pan-cancer machine learning workflow for theranostic target structures
JF - Cancers
N2 - (1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database — representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets.
KW - machine learning
KW - tumor microenvironment
KW - immune infiltration
KW - angiogenesis
KW - mRNA
KW - miRNA
KW - transcriptome
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-305036
SN - 2072-6694
VL - 15
IS - 2
ER -
TY - JOUR
A1 - Tutov, Anna
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Mühlig, Saskia
A1 - Zimmermann, Thomas
A1 - Nose, Naoko
A1 - Koshino, Kazuhiro
A1 - Lapa, Constantin
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Rationalizing the binding modes of PET radiotracers targeting the norepinephrine transporter
JF - Pharmaceutics
N2 - Purpose: A new PET radiotracer \(^{18}\)F-AF78 showing great potential for clinical application has been reported recently. It belongs to a new generation of phenethylguanidine-based norepinephrine transporter (NET)-targeting radiotracers. Although many efforts have been made to develop NET inhibitors as antidepressants, systemic investigations of the structure–activity relationships (SARs) of NET-targeting radiotracers have rarely been performed. Methods: Without changing the phenethylguanidine pharmacophore and 3-fluoropropyl moiety that is crucial for easy labeling, six new analogs of \(^{18}\)F-AF78 with different meta-substituents on the benzene-ring were synthesized and evaluated in a competitive cellular uptake assay and in in vivo animal experiments in rats. Computational modeling of these tracers was established to quantitatively rationalize the interaction between the radiotracers and NET. Results: Using non-radiolabeled reference compounds, a competitive cellular uptake assay showed a decrease in NET-transporting affinity from meta-fluorine to iodine (0.42 and 6.51 µM, respectively), with meta-OH being the least active (22.67 µM). Furthermore, in vivo animal studies with radioisotopes showed that heart-to-blood ratios agreed with the cellular experiments, with AF78(F) exhibiting the highest cardiac uptake. This result correlates positively with the electronegativity rather than the atomic radius of the meta-substituent. Computational modeling studies revealed a crucial influence of halogen substituents on the radiotracer–NET interaction, whereby a T-shaped π–π stacking interaction between the benzene-ring of the tracer and the amino acid residues surrounding the NET binding site made major contributions to the different affinities, in accordance with the pharmacological data. Conclusion: The SARs were characterized by in vitro and in vivo evaluation, and computational modeling quantitatively rationalized the interaction between radiotracers and the NET binding site. These findings pave the way for further evaluation in different species and underline the potential of AF78(F) for clinical application, e.g., cardiac innervation imaging or molecular imaging of neuroendocrine tumors.
KW - positron emission tomography
KW - norepinephrine transporter
KW - sympathetic nervous system
KW - structure–activity relationships
KW - T-shaped π–π stacking
Y1 - 2023
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303949
SN - 1999-4923
VL - 15
IS - 2
ER -
TY - JOUR
A1 - Matsusaka, Yohji
A1 - Chen, Xinyu
A1 - Arias-Loza, Paula
A1 - Werner, Rudolf A.
A1 - Nose, Naoko
A1 - Sasaki, Takanori
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
T1 - In Vivo Functional Assessment of Sodium-Glucose Cotransporters (SGLTs) Using [\(^{18}\)F]Me4FDG PET in Rats
JF - Molecular Imaging
N2 - Background. Mediating glucose absorption in the small intestine and renal clearance, sodium glucose cotransporters (SGLTs) have emerged as an attractive therapeutic target in diabetic patients. A substantial fraction of patients, however, only achieve inadequate glycemic control. Thus, we aimed to assess the potential of the SGLT-targeting PET radiotracer alpha-methyl-4-deoxy-4-[\(^{18}\)F]fluoro-D-glucopyranoside ([\(^{18}\)F]Me4FDG) as a noninvasive intestinal and renal biomarker of SGLT-mediated glucose transport. Methods. We investigated healthy rats using a dedicated small animal PET system. Dynamic imaging was conducted after administration of the reference radiotracer 2-deoxy-2-[\(^{18}\)F]fluoro-D-glucose ([\(^{18}\)F]FDG), or the SGLT-targeting agent, [\(^{18}\)F]Me4FDG either directly into the digestive tract (for assessing intestinal absorption) or via the tail vein (for evaluating kidney excretion). To confirm the specificity of [18F]Me4FDG and responsiveness to treatment, a subset of animals was also pretreated with the SGLT inhibitor phlorizin. In this regard, an intraintestinal route of administration was used to assess tracer absorption in the digestive tract, while for renal assessment, phlorizin was injected intravenously (IV). Results. Serving as reference, intestinal administration of [\(^{18}\)F]FDG led to slow absorption with retention of % of administered radioactivity at 15 min. [\(^{18}\)F]Me4FDG, however, was rapidly absorbed into the blood and cleared from the intestine within 15 min, leading to markedly lower tracer retention of % (). Intraintestinal phlorizin led to marked increase of [\(^{18}\)F]Me4FDG uptake (15 min, %; vs. untreated controls), supporting the notion that this PET agent can measure adequate SGLT inhibition in the digestive tract. In the kidneys, radiotracer was also sensitive to SGLT inhibition. After IV injection, [\(^{18}\)F]Me4FDG reabsorption in the renal cortex was significantly suppressed by phlorizin when compared to untreated animals (%ID/g at 60 min, vs. untreated controls, ; ). Conclusion. As a noninvasive read-out of the concurrent SGLT expression in both the digestive tract and the renal cortex, [\(^{18}\)F]Me4FDG PET may serve as a surrogate marker for treatment response to SGLT inhibition. As such, [\(^{18}\)F]Me4FDG may enable improvement in glycemic control in diabetes by PET-based monitoring strategies.
KW - Sodium-Glucose Cotransporters (SGLTs)
KW - diabetes
KW - rats
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300708
VL - 2022
ER -
TY - JOUR
A1 - Kosmala, Aleksander
A1 - Serfling, Sebastian E.
A1 - Dreher, Niklas
A1 - Lindner, Thomas
A1 - Schirbel, Andreas
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
A1 - Buck, Andreas K.
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
T1 - Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography
JF - Cancers
N2 - (1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05–9.91), 1.42 in the right (range, 0.57–3.06) and 1.41 in the left kidney (range, 0.73–2.97), 1.2 in the heart (range, 0.46–2.59), 0.86 in the spleen (range, 0.55–1.58), 0.65 in the liver (range, 0.31–2.11), and 0.57 in the bone marrow (range, 0.26–0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = −0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.
KW - PET
KW - [\(^{68}\)Ga]Ga-FAPI
KW - theranostics
KW - radioligand therapy
KW - fibroblast activation protein
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275154
SN - 2072-6694
VL - 14
IS - 11
ER -
TY - JOUR
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Koshino, Kazuhiro
A1 - Nose, Naoko
A1 - Mühlig, Saskia
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Lapa, Constantin
A1 - Decker, Michael
A1 - Higuchi, Takahiro
T1 - Molecular Imaging-Derived Biomarker of Cardiac Nerve Integrity - Introducing High NET Affinity PET Probe \(^{18}\)F-AF78
JF - Theranostics
N2 - Background: Radiolabeled agents that are substrates for the norepinephrine transporter (NET) can be used to quantify cardiac sympathetic nervous conditions and have been demonstrated to identify high-risk congestive heart failure (HF) patients prone to arrhythmic events. We aimed to fully characterize the kinetic profile of the novel \(^{18}\)F-labeled NET probe AF78 for PET imaging of the cardiac sympathetic nervous system (SNS) among various species.
Methods: \(^{18}\)F-AF78 was compared to norepinephrine (NE) and established SNS radiotracers by employing in vitro cell assays, followed by an in vivo PET imaging approach with healthy rats, rabbits and nonhuman primates (NHPs). Additionally, chase protocols were performed in NHPs with NET inhibitor desipramine (DMI) and the NE releasing stimulator tyramine (TYR) to investigate retention kinetics in cardiac SNS.
Results: Relative to other SNS radiotracers, 18F-AF78 showed higher transport affinity via NET in a cell-based competitive uptake assay (IC\(^{50}\) 0.42 ± 0.14 µM), almost identical to that of NE (IC\(^{50}\), 0.50 ± 0.16 µM, n.s.). In rabbits and NHPs, initial cardiac uptake was significantly reduced by NET inhibition. Furthermore, cardiac tracer retention was not affected by a DMI chase protocol but was markedly reduced by intermittent TYR chase, thereby suggesting that \(^{18}\)F-AF78 is stored and can be released via the synaptic vesicular turnover process. Computational modeling hypothesized the formation of a T-shaped π-π stacking at the binding site, suggesting a rationale for the high affinity of \(^{18}\)F-AF78.
Conclusion: \(^{18}\)F-AF78 demonstrated high in vitro NET affinity and advantageous in vivo radiotracer kinetics across various species, indicating that \(^{18}\)F-AF78 is an SNS imaging agent with strong potential to guide specific interventions in cardiovascular medicine.
KW - norepinephrine transporter
KW - T-shaped π-π stacking
KW - nonhuman primates
KW - radiotracer kinetics
KW - cardiac innervation imaging
KW - sympathetic nervous system
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300685
VL - 12
IS - 9
SP - 4446
EP - 4458
ER -
TY - JOUR
A1 - Werner, Rudolf A.
A1 - Habacha, Bilêl
A1 - Lütje, Susanne
A1 - Bundschuh, Lena
A1 - Higuchi, Takahiro
A1 - Hartrampf, Philipp
A1 - Serfling, Sebastian E.
A1 - Derlin, Thorsten
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Essler, Markus
A1 - Pienta, Kenneth J.
A1 - Eisenberger, Mario A.
A1 - Markowski, Mark C.
A1 - Shinehouse, Laura
A1 - AbdAllah, Rehab
A1 - Salavati, Ali
A1 - Lodge, Martin A.
A1 - Pomper, Martin G.
A1 - Gorin, Michael A.
A1 - Bundschuh, Ralph A.
A1 - Rowe, Steven P.
T1 - High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL
JF - Molecular Imaging
N2 - No abstract available.
KW - SUV
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300748
VL - 2022
ER -
TY - JOUR
A1 - Matsusaka, Yohji
A1 - Werner, Rudolf A.
A1 - Arias-Loza, Paula
A1 - Nose, Naoko
A1 - Sasaki, Takanori
A1 - Chen, Xinyu
A1 - Lapa, Constantin
A1 - Higuchi, Takahiro
T1 - Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals
JF - Molecular Imaging
N2 - Background. Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods. A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing 99mTc-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as , with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [99mTc]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results. In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion. Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.
KW - SPECT Scanner
KW - medium-sized animals
KW - performance
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300713
VL - 2022
ER -
TY - JOUR
A1 - Serfling, Sebastian E.
A1 - Lapa, Constantin
A1 - Dreher, Niklas
A1 - Hartrampf, Philipp E.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
A1 - Schirbel, Andreas
A1 - Weich, Alexander
A1 - Hahner, Stefanie
A1 - Fassnacht, Martin
A1 - Buck, Andreas K.
A1 - Werner, Rudolf A.
T1 - Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT
JF - Molecular Imaging and Biology
N2 - Background
CXCR4-directed positron emission tomography/computed tomography (PET/CT) has been used as a diagnostic tool in patients with solid tumors. We aimed to determine a potential correlation between tumor burden and radiotracer accumulation in normal organs.
Methods
Ninety patients with histologically proven solid cancers underwent CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT. Volumes of interest (VOIs) were placed in normal organs (heart, liver, spleen, bone marrow, and kidneys) and tumor lesions. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were determined. For CXCR4-positive tumor burden, maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA, defined as SUV\(_{mean}\) x TV), were calculated. We used a Spearman's rank correlation coefficient (ρ) to derive correlative indices between normal organ uptake and tumor burden.
Results
Median SUV\(_{mean}\) in unaffected organs was 5.2 for the spleen (range, 2.44 – 10.55), 3.27 for the kidneys (range, 1.52 – 17.4), followed by bone marrow (1.76, range, 0.84 – 3.98), heart (1.66, range, 0.88 – 2.89), and liver (1.28, range, 0.73 – 2.45). No significant correlation between SUV\(_{max}\) in tumor lesions (ρ ≤ 0.189, P ≥ 0.07), TV (ρ ≥ -0.204, P ≥ 0.06) or FTA (ρ ≥ -0.142, P ≥ 0.18) with the investigated organs was found.
Conclusions
In patients with solid tumors imaged with [\(^{68}\)Ga]Ga-PentixaFor PET/CT, no relevant tumor sink effect was noted. This observation may be of relevance for therapies with radioactive and non-radioactive CXCR4-directed drugs, as with increasing tumor burden, the dose to normal organs may remain unchanged.
KW - CXCR4
KW - C-X-C motif chemokine receptor 4
KW - PET
KW - [68Ga]PentixaFor
KW - [177Lu]/[90Y]PentixaTher
KW - theranostics
KW - endoradiotherapy
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324622
VL - 24
IS - 4
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Higuchi, Takahiro
A1 - Bundschuh, Ralph A.
A1 - Lapa, Constantin
A1 - Serfling, Sebastian E.
A1 - Rowe, Steven P.
A1 - Pomper, Martin G.
A1 - Herrmann, Ken
A1 - Buck, Andreas K.
A1 - Derlin, Thorsten
A1 - Werner, Rudolf A.
T1 - Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers
JF - Molecular Imaging and Biology
N2 - Purpose
For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader’s anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader’s confidence, and its implementation in clinical routine.
Procedures
A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader’s confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen’s d was calculated (small, d = 0.20; large effect, d = 0.80).
Results
Of 22 participants, Pre and Post were returned by 21/22 (95.5%). In total, 14/21 (66.7%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d = − 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader’s confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21).
Conclusions
A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.
KW - PET/CT
KW - neuroendocrine tumor
KW - PRRT
KW - peptide receptor radionuclide therapy
KW - reporting and data system
KW - SSTR-RADS
KW - RADS
Y1 - 2022
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324645
VL - 24
IS - 4
ER -
TY - JOUR
A1 - Weich, Alexander
A1 - Werner, Rudolf A.
A1 - Buck, Andreas K.
A1 - Hartrampf, Philipp E.
A1 - Serfling, Sebastian E.
A1 - Scheurlen, Michael
A1 - Wester, Hans-Jürgen
A1 - Meining, Alexander
A1 - Kircher, Stefan
A1 - Higuchi, Takahiro
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Kircher, Malte
T1 - CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas
JF - Diagnostics
N2 - We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer \(^{68}\)Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard \(^{18}\)F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent \(^{18}\)F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. \(^{68}\)Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while \(^{18}\)F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, \(^{18}\)F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to \(^{68}\)Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard \(^{18}\)F-FDG PET/CT.
KW - CXCR4
KW - NET
KW - NEC
KW - 68Ga-Pentixafor
KW - 18F-FDG
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234231
SN - 2075-4418
VL - 11
IS - 4
ER -
TY - JOUR
A1 - Eissler, Cristoph
A1 - Werner, Rudolf A.
A1 - Arias-Loza, Paula
A1 - Nose, Naoko
A1 - Chen, Xinyu
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Buck, Andreas K.
A1 - Higuchi, Takahiro
T1 - The number of frames on ECG-gated \(^{18}\)F-FDG small animal PET has a significant impact on LV systolic and diastolic functional parameters
JF - Molecular Imaging
N2 - Objectives. This study is aimed at investigating the impact of frame numbers in preclinical electrocardiogram- (ECG-) gated \(^{18}\)F-fluorodeoxyglucose (\(^{18}\)F-FDG) positron emission tomography (PET) on systolic and diastolic left ventricular (LV) parameters in rats. Methods. \(^{18}\)F-FDG PET imaging using a dedicated small animal PET system with list mode data acquisition and continuous ECG recording was performed in diabetic and control rats. The list-mode data was sorted and reconstructed with different numbers of frames (4, 8, 12, and 16) per cardiac cycle into tomographic images. Using an automatic ventricular edge detection software, left ventricular (LV) functional parameters, including ejection fraction (EF), end-diastolic (EDV), and end-systolic volume (ESV), were calculated. Diastolic variables (time to peak filling (TPF), first third mean filling rate (1/3 FR), and peak filling rate (PFR)) were also assessed. Results. Significant differences in multiple parameters were observed among the reconstructions with different frames per cardiac cycle. EDV significantly increased by numbers of frames (353.8 & PLUSMN; 57.7 mu l*, 380.8 & PLUSMN; 57.2 mu l*, 398.0 & PLUSMN; 63.1 mu l*, and 444.8 & PLUSMN; 75.3 mu l at 4, 8, 12, and 16 frames, respectively; *P < 0.0001 vs. 16 frames), while systolic (EF) and diastolic (TPF, 1/3 FR and PFR) parameters were not significantly different between 12 and 16 frames. In addition, significant differences between diabetic and control animals in 1/3 FR and PFR in 16 frames per cardiac cycle were observed (P < 0.005), but not for 4, 8, and 12 frames. Conclusions. Using ECG-gated PET in rats, measurements of cardiac function are significantly affected by the frames per cardiac cycle. Therefore, if you are going to compare those functional parameters, a consistent number of frames should be used.
KW - Myocardial-perfusion SPECT
KW - left-ventricular function
KW - ejection fraction
KW - MRI
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265778
VL - 2021
ER -
TY - JOUR
A1 - Nose, Naoko
A1 - Nogami, Suguru
A1 - Koshino, Kazuhiro
A1 - Chen, Xinyu
A1 - Werner, Rudolf A.
A1 - Kashima, Soki
A1 - Rowe, Steven P.
A1 - Lapa, Constantin
A1 - Fukuchi, Kazuki
A1 - Higuchi, Takahiro
T1 - [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species
JF - Scientific Reports
N2 - Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n=1), rats (n=4), rabbits (n=4) and non-human primates (n=3), via carotid artery in rats (n=4) and non-human primates (n=3), and via intra-myocardial injection in rats (n=5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.
KW - biomarkers
KW - molecular medicine
KW - stem-cell research
KW - stem cells
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260590
VL - 11
IS - 1
ER -
TY - JOUR
A1 - Toyama, Yoshitaka
A1 - Werner, Rudolf A.
A1 - Ruiz-Bedoya, Camilo A.
A1 - Ordonez, Alvaro A.
A1 - Takase, Kei
A1 - Lapa, Constantin
A1 - Jain, Sanjay K.
A1 - Pomper, Martin G.
A1 - Rowe, Steven P.
A1 - Higuchi, Takahiro
T1 - Current and future perspectives on functional molecular imaging in nephro-urology: theranostics on the horizon
JF - Theranostics
N2 - In recent years, a paradigm shift from single-photon-emitting radionuclide radiotracers toward positron-emission tomography (PET) radiotracers has occurred in nuclear oncology. Although PET-based molecular imaging of the kidneys is still in its infancy, such a trend has emerged in the field of functional renal radionuclide imaging. Potentially allowing for precise and thorough evaluation of renal radiotracer urodynamics, PET radionuclide imaging has numerous advantages including precise anatomical co-registration with CT images and dynamic three-dimensional imaging capability. In addition, relative to scintigraphic approaches, PET can allow for significantly reduced scan time enabling high-throughput in a busy PET practice and further reduces radiation exposure, which may have a clinical impact in pediatric populations. In recent years, multiple renal PET radiotracers labeled with C-11, Ga-68, and F-18 have been utilized in clinical studies. Beyond providing a precise non-invasive read-out of renal function, such radiotracers may also be used to assess renal inflammation. This manuscript will provide an overview of renal molecular PET imaging and will highlight the transformation of conventional scintigraphy of the kidneys toward novel, high-resolution PET imaging for assessing renal function. In addition, future applications will be introduced, e.g. by transferring the concept of molecular image-guided diagnostics and therapy (theranostics) to the field of nephrology.
KW - glomerular filtration rate
KW - renal
KW - kidney
KW - renal function
KW - positron emission tomography
KW - nephrology
KW - urology
KW - molecular imaging
KW - theranostics
Y1 - 2021
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260090
VL - 11
IS - 12
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 - 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 - 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 - 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 - 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
A1 - Schmid, Jan-Stefan
A1 - Higuchi, Takahiro
A1 - Javadi, Mehrbod S.
A1 - Rowe, Steven P.
A1 - Märkl, Bruno
A1 - Aulmann, Christoph
A1 - Fassnacht, Martin
A1 - Kroiß, Matthias
A1 - Reiners, Christoph
A1 - Buck, Andreas
A1 - Kreissl, Michael
A1 - Lapa, Constantin
T1 - Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib
JF - Journal of Nuclear Medicine
N2 - Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We
aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment.
Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type).
Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation.
Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance.
Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
KW - positron emission tomography
KW - Medullärer Schilddrüsenkrebs
KW - Positronen-Emissions-Tomografie
KW - medullary thyroid carcinoma
KW - tyrosine kinase inhibitor
KW - vandetanib
KW - 2- deoxy-2-(18F)fluoro-D-glucose
KW - 18F-FDG
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161256
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Jan-Stefan Schmid, Takahiro Higuchi, Mehrbod S. Javadi, Steven P. Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K. Buck, Michael C. Kreissl, Constantin Lapa. Predictive value of 18F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. May 1, 2018;vol. 59 no. 5: 756-761. © SNMMI.
ER -
TY - JOUR
A1 - Werner, Rudolf
A1 - Wakabyashi, Hiroshi
A1 - Chen, Xinyu
A1 - Hirano, Mitsuru
A1 - Shinaji, Tetsuya
A1 - Lapa, Constantin
A1 - Rowe, Steven
A1 - Javadi, Mehrbod
A1 - Higuchi, Takahiro
T1 - Functional renal imaging with \(^{18}\)F-FDS PET in rat models of renal disorders
JF - Journal of Nuclear Medicine
N2 - Background: Precise regional quantitative assessment of renal function is limited with conventional \(^{99m}\)Tc-labeled renal radiotracers. A recent study reported that the positron emission tomography (PET) radiotracer 2-deoxy-2-(\(^{18}\)F-fluorosorbitol (\(^{18}\)F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, (\(^{18}\)F-FDS is available via simple reduction from routinely used 2-deoxy-2-(\(^{18}\)F-fluoro-D-glucose ((\(^{18}\)F-FDG). We aimed to further investigate the potential of (\(^{18}\)F-FDS PET as a functional renal imaging agent using rat models of kidney diseases.
Methods: Two different rat models of renal impairment were investigated: Glycerol induced acute renal failure (ARF) by intramuscular administration of glycerol in hind legs and unilateral ureteral obstruction (UUO) by ligation of the left ureter. 24h after these treatments, dynamic 30 min 18F-FDS PET data were acquired using a dedicated small animal PET system. Urine 18F-FDS radioactivity 30 min after radiotracer injection was measured together with co-injected \(^{99m}\)Tc-diethylenetriaminepentaacetic acid (\(^{99m}\)Tc-DTPA) urine activity. Results: Dynamic PET imaging demonstrated rapid (\(^{18}\)F-FDS accumulation in the renal cortex and rapid radiotracer excretion via kidneys in control healthy rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in ARF rats and UUO-treated kidneys. Measured urine radiotracer concentrations of (\(^{18}\)F-FDS and \(^{99m}\)Tc-DTPA were well correlated (R=0.84, P<0.05).
Conclusions: (\(^{18}\)F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. Advantages of high spatiotemporal resolution of PET imaging and simple tracer production could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.
KW - unilateral ureteral obstruction
KW - Nierenfunktionsstörung
KW - Positronen-Emissions-Tomografie
KW - 18F-FDS
KW - 99mTc-DTPA
KW - PET
KW - renal failure
KW - Glomerular filtration
Y1 - 2018
U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161279
SN - 0161-5505
N1 - This research was originally published in JNM. Rudolf A. Werner, Hiroshi Wakabayashi, Xinyu Chen, Mitsuru Hirano, Tetsuya Shinaji, Constantin Lapa, Steven P. Rowe, Mehrbod S. Javadi and Takahiro Higuchi. Functional renal imaging with 18F-FDS PET in rat models of renal disorders. J Nucl Med. May 1, 2018;vol. 59 no. 5: 828-832. © SNMMI.
ER -