Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach.
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 [68Ga]Pentixafor in comparison to 68Ga-DOTA-D-Phe-Tyr3-octreotide ([68Ga]DOTATOC) and 18F-fluorodeoxyglucose ([18F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [68Ga]DOTATOC, [18F]FDG, and [68Ga]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. [68Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [18F]FDG revealed sites of disease in 10/12 and [68Ga]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 [68Ga]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, [68Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
['Werner|Rudolf A|RA|', 'Weich|Alexander|A|', 'Higuchi|Takahiro|T|', 'Schmid|Jan S|JS|', 'Schirbel|Andreas|A|', 'Lassmann|Michael|M|', 'Wild|Vanessa|V|', 'Rudelius|Martina|M|', 'Kudlich|Theodor|T|', 'Herrmann|Ken|K|', 'Scheurlen|Michael|M|', 'Buck|Andreas K|AK|', 'Kropf|Saskia|S|', 'Wester|Hans-Jürgen|HJ|', 'Lapa|Constantin|C|']
D000368:Aged D000369:Aged, 80 and over D005260:Female D005462:Fluorine Radioisotopes D005710:Gallium Radioisotopes D006801:Humans D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D018358:Neuroendocrine Tumors D000072078:Positron Emission Tomography Computed Tomography D019275:Radiopharmaceuticals D019718:Receptors, CXCR4 D013194:Staining and Labeling
chemokine receptor Neuroendocrine tumor CXCR4 SSTR PET/CT [68Ga]Pentixafor DOTATOC PRRT peptide receptor radionuclide therapy.