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 OPUS4-17026 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 OPUS4-21115 Wissenschaftlicher Artikel Zhou, Xiang; Dierks, Alexander; Kertels, Olivia; Samnick, Samuel; Kircher, Malte; Buck, Andreas K.; Haertle, Larissa; Knorz, Sebastian; Böckle, David; Scheller, Lukas; Messerschmidt, Janin; Barakat, Mohammad; Truger, Marietta; Haferlach, Claudia; Einsele, Hermann; Rasche, Leo; Kortüm, K. Martin; Lapa, Constantin The link between cytogenetics/genomics and imaging patterns of relapse and progression in patients with relapsed/refractory multiple myeloma: a pilot study utilizing 18F-FDG PET/CT Utilizing 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), we performed this pilot study to evaluate the link between cytogenetic/genomic markers and imaging patterns in relapsed/refractory (RR) multiple myeloma (MM). We retrospectively analyzed data of 24 patients with RRMM who were treated at our institution between November 2018 and February 2020. At the last relapse/progression, patients had been treated with a median of three (range 1-10) lines of therapy. Six (25%) patients showed FDG avid extramedullary disease without adjacency to bone. We observed significantly higher maximum standardized uptake values (SUV\(_{max}\)) in patients harboring del(17p) compared with those without del(17p) (p = 0.025). Moreover, a high SUV\(_{max}\) of >15 indicated significantly shortened progression-free survival (PFS) (p = 0.01) and overall survival (OS) (p = 0.0002). One female patient exhibited biallelic TP53 alteration, i.e., deletion and mutation, in whom an extremely high SUV\(_{max}\) of 37.88 was observed. In summary, this pilot study suggested a link between del(17p)/TP53 alteration and high SUV\(_{max}\) on 18F-FDG PET/CT in RRMM patients. Further investigations are highly warranted at this point. 2020 Cancers 12 9 urn:nbn:de:bvb:20-opus-211157 10.3390/cancers12092399 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 OPUS4-11131 Wissenschaftlicher Artikel Lückerath, Katharina; Lapa, Constantin; Spahmann, Annika; Jörg, Gerhard; Samnick, Samuel; Rosenwald, Andreas; Einsele, Herrmann; Knop, Stefan; Buck, Andreas Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology Purpose Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[11C]-methionine (11C-MET) and [18F]-fluoroethyl-L-tyrosine (18F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. Experimental Design To study the utility of 11C-MET, 18F-Fet and 18F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138+ plasma cells were characterized regarding uptake and biomedical features. Results Using myeloma cell lines and patient-derived CD138+ plasma cells, we found that the relative uptake of 11C-MET exceeds that of 18F-FDG 1.5- to 5-fold and that of 18F-Fet 7- to 20-fold. Importantly, 11C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of 11C-MET. Conclusion These data suggest that 11C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with 18F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes. 2013 urn:nbn:de:bvb:20-opus-111319 10.1371/journal.pone.0084840 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 OPUS4-23623 Wissenschaftlicher Artikel Steinhardt, Maximilian Johannes; Zhou, Xiang; Krummenast, Franziska; Meckel, Katharina; Nickel, Katharina; Böckle, David; Messerschmidt, Janin; Knorz, Sebastian; Dierks, Alexander; Heidemeier, Anke; Lapa, Constantin; Einsele, Hermann; Rasche, Leo; Kortüm, Klaus Martin Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab ("Pom-PAD-Dara"), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM. 2020 1-5 International Journal of Immunopathology and Pharmacology 34 urn:nbn:de:bvb:20-opus-236235 10.1177/2058738420980258 Klinik und Poliklinik für Nuklearmedizin OPUS4-17462 unpublished Werner, Rudolf A.; Bundschuh, Ralph A.; Bundschuh, Lena; Fanti, Stefano; Javadi, Mehrbod S.; Higuchi, Takahiro; Weich, A.; Pienta, Kenneth J.; Buck, Andreas K.; Pomper, Martin G.; Gorin, Michael A.; Herrmann, Ken; Lapa, Constantin; Rowe, Steven P. Novel Structured Reporting Systems for Theranostic Radiotracers 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. 2019 Journal of Nuclear Medicine urn:nbn:de:bvb:20-opus-174629 10.2967/jnumed.118.223537 Klinik und Poliklinik für Nuklearmedizin OPUS4-16699 Wissenschaftlicher Artikel Werner, Rudolf A.; Bundschuh, Ralph A.; Bundschuh, Lena; Javadi, Mehrbod S.; Higuchi, Takahiro; Weich, Alexander; Sheikhbahaei, Sara; Pienta, Kenneth J.; Buck, Andreas K.; Pomper, Martin G.; Gorin, Michael A.; Lapa, Constantin; Rowe, Steven P. MI-RADS: Molecular Imaging Reporting and Data Systems - A Generalizable Framework for Targeted Radiotracers with Theranostic Implications Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader's confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems. 2018 Annals of Nuclear Medicine urn:nbn:de:bvb:20-opus-166995 10.1007/s12149-018-1291-7 Klinik und Poliklinik für Nuklearmedizin OPUS4-22498 Wissenschaftlicher Artikel Rasche, Leo; Kumar, Manoj; Gershner, Grant; Samant, Rohan; Van Hemert, Rudy; Heidemeier, Anke; Lapa, Constantin; Bley, Thorsten; Buck, Andreas; McDonald, James; Hillengass, Jens; Epstein, Joshua; Thanendrarajan, Sharmilan; Schinke, Carolina; van Rhee, Frits; Zangari, Maurizio; Barlogie, Bart; Davies, Faith E.; Morgan, Gareth J.; Weinhold, Niels Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis? Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM. 2019 4756-4763 Theranostics 9 16 urn:nbn:de:bvb:20-opus-224982 10.7150/thno.33289 Klinik und Poliklinik für Nuklearmedizin OPUS4-32462 Wissenschaftlicher Artikel Serfling, Sebastian E.; Lapa, Constantin; Dreher, Niklas; Hartrampf, Philipp E.; Rowe, Steven P.; Higuchi, Takahiro; Schirbel, Andreas; Weich, Alexander; Hahner, Stefanie; Fassnacht, Martin; Buck, Andreas K.; Werner, Rudolf A. Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT 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. 2022 659-665 Molecular Imaging and Biology 24 4 urn:nbn:de:bvb:20-opus-324622 10.1007/s11307-022-01717-1 Klinik und Poliklinik für Nuklearmedizin