Imaging of chemokine receptor 4 expression in neuroendocrine tumors - A triple tracer comparative approach

Rudolf A. Werner, Alexander Weich, Takahiro Higuchi, Jan S. Schmid, Andreas Schirbel, Michael Lassmann, Vanessa Wild, Martina Rudelius, Theodor Kudlich, Ken Herrmann, Michael Scheurlen, Andreas K. Buck, Saskia Kropf, Hans Jürgen Wester, Constantin Lapa

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29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1489-1498
Number of pages10
JournalTheranostics
Volume7
Issue number6
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • CXCR4
  • Chemokine receptor
  • DOTATOC
  • Neuroendocrine tumor
  • PET/CT
  • PRRT
  • Peptide receptor radionuclide therapy
  • SSTR
  • [Ga]Pentixafor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    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