Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach

• Published in: Theranostics Vol. 7; no. 6; pp. 1489 - 1498
• Main Authors: Werner, Rudolf A., Weich, Alexander, Higuchi, Takahiro, Schmid, Jan S., Schirbel, Andreas, Lassmann, Michael, Wild, Vanessa, Rudelius, Martina, Kudlich, Theodor, Herrmann, Ken, Scheurlen, Michael, Buck, Andreas K., Kropf, Saskia, Wester, Hans-Jürgen, Lapa, Constantin
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 01.01.2017
• Subjects: Aged; Aged, 80 and over; Female; Fluorine Radioisotopes - administration & dosage; Gallium Radioisotopes - administration & dosage; Humans; Male; Middle Aged; Neoplasm Grading - methods; Neuroendocrine Tumors - diagnostic imaging; Neuroendocrine Tumors - pathology; Positron Emission Tomography Computed Tomography - methods; Radiopharmaceuticals - administration & dosage; Receptors, CXCR4 - analysis; Research Paper; Staining and Labeling - methods; PRRT; DOTATOC; [68Ga]Pentixafor; peptide receptor radionuclide therapy; PET/CT; SSTR; CXCR4; Neuroendocrine tumor; chemokine receptor
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.18754

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 [ Ga]Pentixafor in comparison to Ga-DOTA-D-Phe-Tyr3-octreotide ([ Ga]DOTATOC) and F-fluorodeoxyglucose ([ F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [ Ga]DOTATOC, [ F]FDG, and [ 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. [ Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [ F]FDG revealed sites of disease in 10/12 and [ 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 [ 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, [ 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.