Targeting CXCR4 with [⁶⁸Ga]Pentixafor: A suitable theranostic approach in pleural mesothelioma?

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.