@article{LapaReiterKircheretal.2016,
  author    = {Lapa, Constantin and Reiter, Theresa and Kircher, Malte and Schirbel, Andreas and Werner, Rudolf A. and Pelzer, Theo and Pizarro, Carmen and Skowasch, Dirk and Thomas, Lena and Schlesinger-Irsch, Ulrike and Thomas, Daniel and Bundschuh, Ralph A. and Bauer, Wolfgang R. and Gartner, Florian C.},
  title     = {Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175423},
  pages     = {77807-77814},
  year      = {2016},
  abstract  = {Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25\% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1\% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.},
  language  = {en}
}
@article{WernerBundschuhHiguchietal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and Zs{\´o}t{\´e}r, Norbert and Kroiss, Matthias and Fassnacht, Martin and Buck, Andreas K. and Kreissl, Michael C. and Lapa, Constantin},
  title     = {Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib},
  series = {Endocrine},
  journal   = {Endocrine},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-018-1749-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167910},
  year      = {2018},
  abstract  = {Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{LapaAriasLozaHayakawaetal.2017,
  author    = {Lapa, Constantin and Arias-Loza, Paula and Hayakawa, Nobuyuki and Wakabayashi, Hiroshi and Werner, Rudolf A. and Chen, Xinyu and Shinaji, Tetsuya and Herrmann, Ken and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-017-17148-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159066},
  pages     = {16795},
  year      = {2017},
  abstract  = {Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.},
  language  = {en}
}
@article{WeichWernerBucketal.2021,
  author    = {Weich, Alexander and Werner, Rudolf A. and Buck, Andreas K. and Hartrampf, Philipp E. and Serfling, Sebastian E. and Scheurlen, Michael and Wester, Hans-J{\"u}rgen and Meining, Alexander and Kircher, Stefan and Higuchi, Takahiro and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin and Kircher, Malte},
  title     = {CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas},
  series = {Diagnostics},
  volume    = {11},
  journal   = {Diagnostics},
  number    = {4},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics11040605},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234231},
  year      = {2021},
  abstract  = {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-na{\"i}ve 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.},
  language  = {en}
}
@article{WernerEisslerHayakawaetal.2018,
  author    = {Werner, Rudolf A. and Eissler, Christoph and Hayakawa, Nobuyuki and Arias-Loza, Paula and Wakabayashi, Hiroshi and Javadi, Mehrbod S. and Chen, Xinyu and Shinaji, Tetsuya and Lapa, Constantin and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET},
  series = {Scientific Reports},
  volume    = {8},
  journal   = {Scientific Reports},
  number    = {17631},
  doi       = {10.1038/s41598-018-35986-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171765},
  year      = {2018},
  abstract  = {In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5\%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.},
  language  = {en}
}
@article{LenschowWennmannHendricksetal.2022,
  author    = {Lenschow, Christina and Wennmann, Andreas and Hendricks, Anne and Germer, Christoph-Thomas and Fassnacht, Martin and Buck, Andreas and Werner, Rudolf A. and Plassmeier, Lars and Schlegel, Nicolas},
  title     = {Questionable value of [\(^{99m}\)Tc]-sestamibi scintigraphy in patients with pHPT and negative ultrasound},
  series = {Langenbeck's Archives of Surgery},
  volume    = {407},
  journal   = {Langenbeck's Archives of Surgery},
  number    = {8},
  doi       = {10.1007/s00423-022-02648-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323926},
  pages     = {3661-3669},
  year      = {2022},
  abstract  = {Purpose A successful focused surgical approach in primary hyperparathyroidism (pHPT) relies on accurate preoperative localization of the parathyroid adenoma (PA). Most often, ultrasound is followed by [\(^{99m}\)Tc]-sestamibi scintigraphy, but the value of this approach is disputed. Here, we evaluated the diagnostic approach in patients with surgically treated pHPT in our center with the aim to further refine preoperative diagnostic procedures. Methods A single-center retrospective analysis of patients with pHPT from 01/2005 to 08/2021 was carried out followed by evaluation of the preoperative imaging modalities to localize PA. The localization of the PA had to be confirmed intraoperatively by the fresh frozen section and significant dropping of the intraoperative parathyroid hormone (PTH) levels. Results From 658 patients diagnosed with pHPT, 30 patients were excluded from the analysis because of surgery for recurrent or persistent disease. Median age of patients was 58.0 (13-93) years and 71\% were female. Neck ultrasound was carried out in 91.7\% and localized a PA in 76.6\%. In 23.4\% (135/576) of the patients, preoperative neck ultrasound did not detect a PA. In this group, [\(^{99m}\)Tc]-sestamibi correctly identified PA in only 25.4\% of patients. In contrast, in the same cohort, the use of [\(^{11}\)C]-methionine or [\(^{11}\)C]-choline PET resulted in the correct identification of PA in 79.4\% of patients (OR 13.23; 95\% CI 5.24-33.56). Conclusion [\(^{11}\)C]-Methionine or [\(^{11}\)C]-choline PET/CT are superior second-line imaging methods to select patients for a focused surgical approach when previous ultrasound failed to identify PA.},
  language  = {en}
}
@article{WernerSayehliHaenscheidetal.2023,
  author    = {Werner, Rudolf A. and Sayehli, Cyrus and H{\"a}nscheid, Heribert and Higuchi, Takahiro and Serfling, Sebastian E. and Fassnacht, Martin and Goebeler, Maria-Elisabeth and Buck, Andreas K. and Kroiss, Matthias},
  title     = {Successful combination of selpercatinib and radioiodine after pretherapeutic dose estimation in RET-altered thyroid carcinoma},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {50},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {6},
  doi       = {10.1007/s00259-022-06061-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324435},
  pages     = {1833-1834},
  year      = {2023},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{SerflingLapaDreheretal.2022,
  author    = {Serfling, Sebastian E. and Lapa, Constantin and Dreher, Niklas and Hartrampf, Philipp E. and Rowe, Steven P. and Higuchi, Takahiro and Schirbel, Andreas and Weich, Alexander and Hahner, Stefanie and Fassnacht, Martin and Buck, Andreas K. and Werner, Rudolf A.},
  title     = {Impact of tumor burden on normal organ distribution in patients imaged with CXCR4-targeted [\(^{68}\)Ga]Ga-PentixaFor PET/CT},
  series = {Molecular Imaging and Biology},
  volume    = {24},
  journal   = {Molecular Imaging and Biology},
  number    = {4},
  doi       = {10.1007/s11307-022-01717-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324622},
  pages     = {659-665},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@article{BuckSerflingLindneretal.2022,
  author    = {Buck, Andreas K. and Serfling, Sebastian E. and Lindner, Thomas and H{\"a}nscheid, Heribert and Schirbel, Andreas and Hahner, Stefanie and Fassnacht, Martin and Einsele, Hermann and Werner, Rudolf A.},
  title     = {CXCR4-targeted theranostics in oncology},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  doi       = {10.1007/s00259-022-05849-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324545},
  pages     = {4133-4144},
  year      = {2022},
  abstract  = {A growing body of literature reports on the upregulation of C-X-C motif chemokine receptor 4 (CXCR4) in a variety of cancer entities, rendering this receptor as suitable target for molecular imaging and endoradiotherapy in a theranostic setting. For instance, the CXCR4-targeting positron emission tomography (PET) agent [\(^{68}\)Ga]PentixaFor has been proven useful for a comprehensive assessment of the current status quo of solid tumors, including adrenocortical carcinoma or small-cell lung cancer. In addition, [\(^{68}\)Ga]PentixaFor has also provided an excellent readout for hematological malignancies, such as multiple myeloma, marginal zone lymphoma, or mantle cell lymphoma. PET-based quantification of the CXCR4 capacities in vivo allows for selecting candidates that would be suitable for treatment using the theranostic equivalent [\(^{177}\)Lu]/[\(^{90}\)Y]PentixaTher. This CXCR4-directed theranostic concept has been used as a conditioning regimen prior to hematopoietic stem cell transplantation and to achieve sufficient anti-lymphoma/-tumor activity in particular for malignant tissues that are highly sensitive to radiation, such as the hematological system. Increasing the safety margin, pretherapeutic dosimetry is routinely performed to determine the optimal activity to enhance therapeutic efficacy and to reduce off-target adverse events. The present review will provide an overview of current applications for CXCR4-directed molecular imaging and will introduce the CXCR4-targeted theranostic concept for advanced hematological malignancies.},
  language  = {en}
}