Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-32464 Wissenschaftlicher Artikel Weich, Alexander; Higuchi, Takahiro; Bundschuh, Ralph A.; Lapa, Constantin; Serfling, Sebastian E.; Rowe, Steven P.; Pomper, Martin G.; Herrmann, Ken; Buck, Andreas K.; Derlin, Thorsten; Werner, Rudolf A. Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers 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. 2022 631-640 Molecular Imaging and Biology 24 4 urn:nbn:de:bvb:20-opus-324645 10.1007/s11307-022-01712-6 Klinik und Poliklinik für Nuklearmedizin OPUS4-23365 Wissenschaftlicher Artikel Wevrett, Jill; Fenwick, Andrew; Scuffham, James; Johansson, Lena; Gear, Jonathan; Schlögl, Susanne; Segbers, Marcel; Sjögreen-Gleisner, Katarina; Solný, Pavel; Lassmann, Michael; Tipping, Jill; Nisbet, Andrew Inter-comparison of quantitative imaging of lutetium-177 (\(^{177}\)Lu) in European hospitals Background This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (\(^{177}\)Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources—they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. Results The volumes reported by the participants for the inner section of the source were all within 29% of the true value and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. Conclusions A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. This paper presents a method to assess consistency between sites using different calibration and segmentation methods. 2018 EJNMMI Physics 5 urn:nbn:de:bvb:20-opus-233658 10.1186/s40658-018-0213-z Klinik und Poliklinik für Nuklearmedizin OPUS4-17731 Wissenschaftlicher Artikel Werner, Rudolf A.; Beykan, Seval; Higuchi, Takahiro; Lückerath, Katharina; Weich, Alexander; Scheurlen, Michael; Bluemel, Christina; Herrmann, Ken; Buck, Andreas K.; Lassmann, Michael; Lapa, Constantin; Hänscheid, Heribert The impact of \(^{177}\)Lu-octreotide therapy on \(^{99m}\)Tc-MAG3 clearance is not predictive for late nephropathy 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. 2016 41233-41241 Oncotarget 7 27 urn:nbn:de:bvb:20-opus-177318 10.18632/oncotarget.9775 Klinik und Poliklinik für Nuklearmedizin OPUS4-17026 Wissenschaftlicher Artikel Werner, Rudolf A.; Weich, Alexander; Kircher, Malte; Solnes, Lilja B.; Javadi, Mehrbod S.; Higuchi, Takahiro; Buck, Andreas K.; Pomper, Martin G.; Rowe, Steven; Lapa, Constantin The theranostic promise for neuroendocrine tumors in the late 2010s - Where do we stand, where do we go? 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. 2018 6088-6100 Theranostics 8 22 urn:nbn:de:bvb:20-opus-170264 Klinik und Poliklinik für Nuklearmedizin OPUS4-16129 Wissenschaftlicher Artikel Werner, Rudolf; Solnes, Lilja; Javadi, Mehrbod; Weich, Alexander; Gorin, Michael; Pienta, Kenneth; Higuchi, Takahiro; Buck, Andreas; Pomper, Martin; Rowe, Steven; Lapa, Constantin SSTR-RADS Version 1.0 as a Reporting System for SSTR-PET Imaging and Selection of Potential PRRT Candidates: A Proposed Standardization Framework Reliable standards and criteria for somatostatin receptor (SSTR) positron emission tomography (PET) are still lacking. We herein propose a structured reporting system on a 5-point scale for SSTR-PET imaging, titled SSTR-RADS version 1.0, which might serve as a standardized assessment for both diagnosis and treatment planning in neuroendocrine tumors (NET). SSTR-RADS could guide the imaging specialist in interpreting SSTR-PET scans, facilitate communication with the referring clinician so that appropriate work-up for equivocal findings is pursued, and serve as a reliable tool for patient selection for planned Peptide Receptor Radionuclide Therapy. 2018 Journal of Nuclear Medicine urn:nbn:de:bvb:20-opus-161298 10.2967/jnumed.117.206631 Klinik und Poliklinik für Nuklearmedizin OPUS4-16116 Konferenzveröffentlichung Werner, Rudolf; Lapa, Constantin; Buck, Andreas; Lassmann, Michael; Hänscheid, Heribert Less is sometimes more - Accurate Dose Mapping after Endoradiotherapy with \(^{177}\)Lu-DOTATATE/-TOC by One-Single Measurement after 96 h No abstract available. Society of Nuclear Medicine and Molecular Imaging 2017 247 Journal of Nuclear Medicine 58 No. Supplement 1 urn:nbn:de:bvb:20-opus-161168 Klinik und Poliklinik für Nuklearmedizin OPUS4-15898 Wissenschaftlicher Artikel Lapa, Constantin; Kircher, Malte; Hänscheid, Heribert; Schirbel, Andreas; Grigoleit, Götz Ulrich; Klinker, Erdwine; Böck, Markus; Samnick, Samuel; Pelzer, Theo; Buck, Andreas K Peptide receptor radionuclide therapy as a new tool in treatment-refractory sarcoidosis - initial experience in two patients Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve virtually all organ systems. Whereas most patients present without symptoms, progressive and disabling organ failure can occur in up to 10% of subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide therapy (PRRT) has recently received market authorization for treatment of SSTR-positive neuroendocrine tumors. Methods: We describe the first case series comprising two patients with refractory multi-organ involvement of sarcoidosis who received 4 cycles of PRRT. Results: PRRT was well-tolerated without any acute adverse effects. No relevant toxicities could be recorded during follow-up. Therapy resulted in partial response accompanied by a pronounced reduction in pain (patient #1) and stable disease regarding morphology as well as disease activity (patient #2), respectively. Conclusion: Peptide receptor radionuclide therapy in sarcoidosis is feasible and might be a new valuable tool in patients with otherwise treatment-refractory disease. Given the long experience with and good tolerability of PRRT, further evaluation of this new treatment option for otherwise treatment-refractory sarcoidosis in larger patient cohorts is warranted. 2018 644–649 Theranostics 8 3 urn:nbn:de:bvb:20-opus-158983 10.7150/thno.22161 Klinik und Poliklinik für Nuklearmedizin OPUS4-15800 Wissenschaftlicher Artikel Werner, Rudolf A.; Weich, Alexander; Higuchi, Takahiro; Schmid, Jan S.; Schirbel, Andreas; Lassmann, Michael; Wild, Vanessa; Rudelius, Martina; Kudlich, Theodor; Herrmann, Ken; Scheurlen, Michael; Buck, Andreas K.; Kropf, Saskia; Wester, Hans-Jürgen; Lapa, Constantin Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors. 2017 1489-1498 Theranostics 7 6 urn:nbn:de:bvb:20-opus-158008 10.7150/thno.18754 Klinik und Poliklinik für Nuklearmedizin OPUS4-14688 Wissenschaftlicher Artikel Beykan, Seval; Dam, Jan S.; Eberlein, Uta; Kaufmann, Jens; Kjærgaard, Benedict; Jødal, Lars; Bouterfa, Hakim; Bejot, Romain; Lassmann, Michael; Jensen, Svend Borup \(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model Background \(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications. Results \(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. Conclusions The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range. 2016 EJNMMI Research 6 50 urn:nbn:de:bvb:20-opus-146888 10.1186/s13550-016-0204-9 Klinik und Poliklinik für Nuklearmedizin OPUS4-12496 Wissenschaftlicher Artikel Lapa, Constantin; Werner, Rudolf A.; Bluemel, Christina; Lueckerath, Katharina; Muegge, Dirk O.; Strate, Alexander; Haenscheid, Heribert; Schirbel, Andreas; Allen-Auerbach, Martin S.; Bundschuh, Ralph A.; Buck, Andreas K.; Herrmann, Ken Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of \(^{177}Lu\)-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = −0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying 'high-risk' patients prone to PRRT. 2014 EJNMMI Research 4 74 urn:nbn:de:bvb:20-opus-124963 10.1186/s13550-014-0074-y Institut für Klinische Biochemie und Pathobiochemie