@article{LapaSchrederSchirbeletal.2017, author = {Lapa, Constantin and Schreder, Martin and Schirbel, Andreas and Samnick, Samuel and Kort{\"u}m, Klaus Martin and Herrmann, Ken and Kropf, Saskia and Einsele, Herrmann and Buck, Andreas K. and Wester, Hans-J{\"u}rgen and Knop, Stefan and L{\"u}ckerath, Katharina}, title = {[\(^{68}\)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [\(^{18}\)F]FDG and laboratory values}, series = {Theranostics}, volume = {7}, journal = {Theranostics}, number = {1}, doi = {10.7150/thno.16576}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172106}, pages = {205-212}, year = {2017}, abstract = {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.}, language = {en} } @article{LapaHerrmannSchirbeletal.2017, author = {Lapa, Constantin and Herrmann, Ken and Schirbel, Andreas and H{\"a}nscheid, Heribert and L{\"u}ckerath, Katharina and Schottelius, Margret and Kircher, Malte and Werner, Rudolf A. and Schreder, Martin and Samnick, Samuel and Kropf, Saskia and Knop, Stefan and Buck, Andreas K. and Einsele, Hermann and Wester, Hans-Juergen and Kort{\"u}m, K. Martin}, title = {CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma}, series = {Theranostics}, volume = {7}, journal = {Theranostics}, number = {6}, doi = {10.7150/thno.19050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172095}, pages = {1589-1597}, year = {2017}, abstract = {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.}, language = {en} } @article{LapaGarciaVellosoLueckerathetal.2017, author = {Lapa, Constantin and Garcia-Velloso, Maria J. and L{\"u}ckerath, Katharina and Samnick, Samuel and Schreder, Martin and Otero, Paula Rodriguez and Schmid, Jan-Stefan and Herrmann, Ken and Knop, Stefan and Buck, Andreas K. and Einsele, Hermann and San-Miguel, Jesus and Kort{\"u}m, Klaus Martin}, title = {\(^{11}\)C-methionine-PET in multiple myeloma: a combined study from two different institutions}, series = {Theranostics}, volume = {7}, journal = {Theranostics}, number = {11}, doi = {10.7150/thno.20491}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172038}, pages = {2956-2964}, year = {2017}, abstract = {\(^{11}\)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 W{\"u}rzburg, 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.}, language = {en} } @unpublished{WernerBundschuhBundschuhetal.2019, author = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Fanti, Stefano and Javadi, Mehrbod S. and Higuchi, Takahiro and Weich, A. and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Herrmann, Ken and Lapa, Constantin and Rowe, Steven P.}, title = {Novel Structured Reporting Systems for Theranostic Radiotracers}, series = {Journal of Nuclear Medicine}, journal = {Journal of Nuclear Medicine}, issn = {0161-5505}, doi = {10.2967/jnumed.118.223537}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174629}, year = {2019}, abstract = {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.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{LapaWernerBluemeletal.2014, author = {Lapa, Constantin and Werner, Rudolf A. and Bluemel, Christina and Lueckerath, Katharina and Muegge, Dirk O. and Strate, Alexander and Haenscheid, Heribert and Schirbel, Andreas and Allen-Auerbach, Martin S. and Bundschuh, Ralph A. and Buck, Andreas K. and Herrmann, Ken}, title = {Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy}, series = {EJNMMI Research}, volume = {4}, journal = {EJNMMI Research}, number = {74}, doi = {10.1186/s13550-014-0074-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124963}, year = {2014}, abstract = {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.}, language = {en} } @article{HeinzeSchirbelNannenetal.2021, author = {Heinze, Britta and Schirbel, Andreas and Nannen, Lukas and Michelmann, David and Hartrampf, Philipp E. and Bluemel, Christina and Schneider, Magdalena and Herrmann, Ken and Haenscheid, Heribert and Fassnacht, Martin and Buck, Andreas K. and Hahner, Stefanie}, title = {Novel CYP11B-ligand [\(^{123/131}\)I]IMAZA as promising theranostic tool for adrenocortical tumors: comprehensive preclinical characterization and first clinical experience}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {49}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {1}, issn = {1619-7089}, doi = {10.1007/s00259-021-05477-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265606}, pages = {301-310}, year = {2021}, abstract = {Purpose Adrenal tumors represent a diagnostic and therapeutic challenge. Promising results have been obtained through targeting the cytochrome P450 enzymes CYP11B1 and CYP11B2 for molecular imaging, and [\(^{123/131}\)I]iodometomidate ([\(^{123/131}\)I]IMTO) has even been successfully introduced as a theranostic agent. As this radiopharmaceutical shows rapid metabolic inactivation, we aimed at developing new improved tracers. Methods Several IMTO derivatives were newly designed by replacing the unstable methyl ester by different carboxylic esters or amides. The inhibition of aldosterone and cortisol synthesis was tested in different adrenocortical cell lines. The corresponding radiolabeled compounds were assessed regarding their stability, in vitro cell uptake, in vivo biodistribution in mice, and their binding specificity to cryosections of human adrenocortical and non-adrenocortical tissue. Furthermore, a first investigation was performed in patients with known metastatic adrenal cancer using both [\(^{123}\)I]IMTO and the most promising compound (R)-1-[1-(4-[\(^{123/}\)I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinylamide ([\(^{123}\)I]IMAZA) for scintigraphy. Subsequently, a first endoradiotherapy with [\(^{131}\)I]IMAZA in one of these patients was performed. Results We identified three analogues to IMTO with high-affinity binding to the target enzymes and comparable or higher metabolic stability and very high and specific accumulation in adrenocortical cells in vitro and in vivo. Labeled IMAZA exhibited superior pharmacokinetic and imaging properties compared to IMTO in mice and 3 patients, too. An endoradiotherapy with [\(^{131}\)I]IMAZA induced a 21-month progression-free interval in a patient with rapidly progressing ACC prior this therapy. Conclusion We developed the new radiopharmaceutical [\(^{123/131}\)I]IMAZA with superior properties compared to the reference compound IMTO and promising first experiences in humans.}, language = {en} } @article{WeichHiguchiBundschuhetal.2022, author = {Weich, Alexander and Higuchi, Takahiro and Bundschuh, Ralph A. and Lapa, Constantin and Serfling, Sebastian E. and Rowe, Steven P. and Pomper, Martin G. and Herrmann, Ken and Buck, Andreas K. and Derlin, Thorsten and Werner, Rudolf A.}, title = {Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers}, series = {Molecular Imaging and Biology}, volume = {24}, journal = {Molecular Imaging and Biology}, number = {4}, doi = {10.1007/s11307-022-01712-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324645}, pages = {631-640}, year = {2022}, abstract = {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.}, language = {en} }