@article{BreunMonoranuKessleretal.2019,
  author    = {Breun, Maria and Monoranu, Camelia M. and Kessler, Almuth F. and Matthies, Cordula and L{\"o}hr, Mario and Hagemann, Carsten and Schirbel, Andreas and Rowe, Steven P. and Pomper, Martin G. and Buck, Andreas K. and Wester, Hans-J{\"u}rgen and Ernestus, Ralf-Ingo and Lapa, Constantin},
  title     = {[\(^{68}\)Ga]-Pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  number    = {503},
  doi       = {10.3389/fonc.2019.00503},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201863},
  year      = {2019},
  abstract  = {We have recently demonstrated CXCR4 overexpression in vestibular schwannomas (VS). This study investigated the feasibility of CXCR4-directed positron emission tomography/computed tomography (PET/CT) imaging of VS using the radiolabeled chemokine ligand [\(^{68}\)Ga]Pentixafor. Methods: 4 patients with 6 primarily diagnosed or pre-treated/observed VS were enrolled. All subjects underwent [\(^{68}\)Ga]Pentixafor PET/CT prior to surgical resection. Images were analyzed visually and semi-quantitatively for CXCR4 expression including calculation of tumor-to-background ratios (TBR). Immunohistochemistry served as standard of reference in three patients. Results: [\(^{68}\)Ga]Pentixafor PET/CT was visually positive in all cases. SUV\(_{mean}\) and SUV\(_{max}\) were 3.0 ± 0.3 and 3.8 ± 0.4 and TBR\(_{mean}\) and TBR\(_{max}\) were 4.0 ± 1.4 and 5.0 ± 1.7, respectively. Histological analysis confirmed CXCR4 expression in tumors. Conclusion: Non-invasive imaging of CXCR4 expression using [\(^{68}\)Ga]Pentixafor PET/CT of VS is feasible and could prove useful for in vivo assessment of CXCR4 expression.},
  language  = {en}
}
@article{LapaLueckerathKleinleinetal.2016,
  author    = {Lapa, Constantin and L{\"u}ckerath, Katharina and Kleinlein, Irene and Monoranu, Camelia Maria and Linsenmann, Thomas and Kessler, Almuth F. and Rudelius, Martina and Kropf, Saskia and Buck, Andreas K. and Ernestus, Ralf-Ingo and Wester, Hans-J{\"u}rgen and L{\"o}hr, Mario and Herrmann, Ken},
  title     = {\(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma},
  series = {Theranostics},
  volume    = {6},
  journal   = {Theranostics},
  number    = {3},
  doi       = {10.7150/thno.13986},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168174},
  pages     = {428-434},
  year      = {2016},
  abstract  = {Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. \(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.},
  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{WernerWeichHiguchietal.2017,
  author    = {Werner, Rudolf A. and Weich, Alexander and Higuchi, Takahiro and Schmid, Jan S. and Schirbel, Andreas and Lassmann, Michael and Wild, Vanessa and Rudelius, Martina and Kudlich, Theodor and Herrmann, Ken and Scheurlen, Michael and Buck, Andreas K. and Kropf, Saskia and Wester, Hans-J{\"u}rgen and Lapa, Constantin},
  title     = {Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach},
  series = {Theranostics},
  volume    = {7},
  journal   = {Theranostics},
  number    = {6},
  doi       = {10.7150/thno.18754},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158008},
  pages     = {1489-1498},
  year      = {2017},
  abstract  = {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.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{PhilippAbbrederisHerrmannKnopetal.2015,
  author    = {Philipp-Abbrederis, Kathrin and Herrmann, Ken and Knop, Stefan and Schottelius, Margret and Eiber, Matthias and L{\"u}ckerath, Katharina and Pietschmann, Elke and Habringer, Stefan and Gerngroß, Carlos and Franke, Katharina and Rudelius, Martina and Schirbel, Andreas and Lapa, Constantin and Schwamborn, Kristina and Steidle, Sabine and Hartmann, Elena and Rosenwald, Andreas and Kropf, Saskia and Beer, Ambros J and Peschel, Christian and Einsele, Hermann and Buck, Andreas K and Schwaiger, Markus and G{\"o}tze, Katharina and Wester, Hans-J{\"u}rgen and Keller, Ulrich},
  title     = {In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma},
  series = {EMBO Molecular Medicine},
  volume    = {7},
  journal   = {EMBO Molecular Medicine},
  number    = {4},
  doi       = {10.15252/emmm.201404698},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148738},
  pages     = {477-487},
  year      = {2015},
  abstract  = {CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.},
  language  = {en}
}
@article{LapaKircherSchirbeletal.2017,
  author    = {Lapa, Constantin and Kircher, Stefan and Schirbel, Andreas and Rosenwald, Andreas and Kropf, Saskia and Pelzer, Theo and Walles, Thorsten and Buck, Andreas K. and Weber, Wolfgang A. and Wester, Hans-Juergen and Herrmann, Ken and L{\"u}ckerath, Katharina},
  title     = {Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?},
  series = {Oncotarget},
  volume    = {8},
  journal   = {Oncotarget},
  number    = {57},
  doi       = {10.18632/oncotarget.18235},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169989},
  pages     = {96732-96737},
  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. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.},
  language  = {en}
}
@article{HerrmannBuckSchusteretal.2014,
  author    = {Herrmann, Ken and Buck, Andreas K. and Schuster, Tibor and Abbrederis, Kathrin and Bl{\"u}mel, Christina and Santi, Ivan and Rudelius, Martina and Wester, Hans-J{\"u}rgen and Peschel, Christian and Schwaiger, Markus and Dechow, Tobias and Keller, Ulrich},
  title     = {Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {12},
  issn      = {1949-2553},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120659},
  pages     = {4050-59},
  year      = {2014},
  abstract  = {Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.},
  language  = {en}
}