Targeting CXCR4 with [68Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?
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Constantin Lapa1, Stefan Kircher2, Andreas Schirbel1, Andreas Rosenwald2, Saskia Kropf3, Theo Pelzer4, Thorsten Walles5, Andreas K. Buck1, Wolfgang A. Weber6, Hans-Juergen Wester7, Ken Herrmann1,8 and Katharina Lückerath1
1Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
2Institute of Pathology, University of Würzburg, Comprehensive Cancer Center Mainfranken (CCCMF), Würzburg, Germany
3Scintomics GmbH, Fürstenfeldbruck, Germany
4Department of Internal Medicine I, Division of Pulmonology, Universitätsklinikum Würzburg, Würzburg, Germany
5Department of Thoracic Surgery, University Hospital Magdeburg, Magdeburg, Germany
6Molecular Imaging and Therapy Service, Memorial Sloan-Kettering Cancer Center and Weill-Cornell Medical College, New York, New York, USA
7Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany
8Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
Constantin Lapa, email: [email protected]
Keywords: PET, CXCR4, [68Ga] pentixafor, pleural mesothelioma, theranostics
Received: March 29, 2017 Accepted: May 15, 2017 Published: May 27, 2017
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 [68Ga]Pentixafor in malignant pleural mesothelioma.
Six patients with pleural mesothelioma underwent [68Ga]Pentixafor-PET/CT. 2′-[18F]fluoro-2′-deoxy-D-glucose ([18F]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 [18F]FDG-PET depicted active lesions in all patients, [68Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [68Ga]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.
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