@article{LewisHabringerKircheretal.2021,
  author    = {Lewis, Richard and Habringer, Stefan and Kircher, Malte and Hefter, Maike and Peuker, Caroline Anna and Werner, Rudolf and Ademaj-Kospiri, Val{\"e}za and G{\"a}ble, Alexander and Weber, Wolfgang and Wester, Hans-J{\"u}rgen and Buck, Andreas and Herhaus, Peter and Lapa, Constantin and Keller, Ulrich},
  title     = {Investigation of spleen CXCR4 expression by [68Ga]Pentixafor PET in a cohort of 145 solid cancer patients},
  series = {EJNMMI Research},
  volume    = {11},
  journal   = {EJNMMI Research},
  doi       = {10.1186/s13550-021-00822-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363820},
  year      = {2021},
  abstract  = {Background The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([68Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed. Results We investigated the hypothesis that enhanced spleen [68Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [68Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [68Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [68Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [68Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer. Conclusion Spleen [68Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [68Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.},
  language  = {en}
}
@article{WernerKircherHiguchietal.2019,
  author    = {Werner, Rudolf A. and Kircher, Stefan and Higuchi, Takahiro and Kircher, Malte and Schirbel, Andreas and Wester, Hans-J{\"u}rgen and Buck, Andreas K. and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin},
  title     = {CXCR4-directed imaging in solid tumors},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  number    = {770},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2019.00770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195678},
  year      = {2019},
  abstract  = {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-na{\"i}ve 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-na{\"i}ve 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.},
  language  = {en}
}