Journal
EMBO MOLECULAR MEDICINE
Volume 7, Issue 4, Pages 477-487Publisher
WILEY
DOI: 10.15252/emmm.201404698
Keywords
chemokine receptor; CXCR4; in vivo imaging; multiple myeloma; positron emission tomography
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB824]
- Deutsche Krebshilfe [111305]
- DFG [KE 222/7-1]
- German Cancer Consortium (DKTK)
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CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [Ga-68]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [Ga-68]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [Ga-68]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [F-18]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [Ga-68]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
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