Theranostics 2017; 7(6):1489-1498. doi:10.7150/thno.18754 This issue Cite
1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany;
2. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States;
3. Else-Kröner-Forschungskolleg, Interdisciplinary Center for Clinical Research, University of Würzburg, Würzburg, Germany;
4. Department of Internal Medicine II, Gastroenterology, University Hospital Würzburg, Würzburg, Germany;
5. Comprehensive Cancer Center Mainfranken, University Hospital Würzburg, Würz-burg, Germany;
6. Institute for Pathology, University of Würzburg, Würzburg, Germany;
7. Department of Nuclear Medicine, University Hospital Essen, Essen, Germany;
8. Scintomics GmbH, Fürstenfeldbruck, Germany;
9. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
* Both authors contributed equally to this work.
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.
Keywords: Neuroendocrine tumor, [68Ga]Pentixafor, CXCR4, chemokine receptor, PET/CT, SSTR, DOTATOC, PRRT, peptide receptor radionuclide therapy.