Theranostics 2017; 7(6):1489-1498. doi:10.7150/thno.18754 This issue Cite

Research Paper

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

Rudolf A. Werner1, 2, 3*, Alexander Weich4, 5*, Takahiro Higuchi1, Jan S. Schmid1, Andreas Schirbel1, Michael Lassmann1, Vanessa Wild6, Martina Rudelius5, 6, Theodor Kudlich4, Ken Herrmann7, Michael Scheurlen4, Andreas K. Buck1, Saskia Kropf8, Hans-Jürgen Wester9, Constantin Lapa1✉

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.

Citation:
Werner RA, Weich A, Higuchi T, Schmid JS, Schirbel A, Lassmann M, Wild V, Rudelius M, Kudlich T, Herrmann K, Scheurlen M, Buck AK, Kropf S, Wester HJ, Lapa C. Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach. Theranostics 2017; 7(6):1489-1498. doi:10.7150/thno.18754. https://www.thno.org/v07p1489.htm
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Abstract

Graphic abstract

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.


Citation styles

APA
Werner, R.A., Weich, A., Higuchi, T., Schmid, J.S., Schirbel, A., Lassmann, M., Wild, V., Rudelius, M., Kudlich, T., Herrmann, K., Scheurlen, M., Buck, A.K., Kropf, S., Wester, H.J., Lapa, C. (2017). Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach. Theranostics, 7(6), 1489-1498. https://doi.org/10.7150/thno.18754.

ACS
Werner, R.A.; Weich, A.; Higuchi, T.; Schmid, J.S.; Schirbel, A.; Lassmann, M.; Wild, V.; Rudelius, M.; Kudlich, T.; Herrmann, K.; Scheurlen, M.; Buck, A.K.; Kropf, S.; Wester, H.J.; Lapa, C. Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach. Theranostics 2017, 7 (6), 1489-1498. DOI: 10.7150/thno.18754.

NLM
Werner RA, Weich A, Higuchi T, Schmid JS, Schirbel A, Lassmann M, Wild V, Rudelius M, Kudlich T, Herrmann K, Scheurlen M, Buck AK, Kropf S, Wester HJ, Lapa C. Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach. Theranostics 2017; 7(6):1489-1498. doi:10.7150/thno.18754. https://www.thno.org/v07p1489.htm

CSE
Werner RA, Weich A, Higuchi T, Schmid JS, Schirbel A, Lassmann M, Wild V, Rudelius M, Kudlich T, Herrmann K, Scheurlen M, Buck AK, Kropf S, Wester HJ, Lapa C. 2017. Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach. Theranostics. 7(6):1489-1498.

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