In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma

EMBO Molecular Medicine
Kathrin Philipp-AbbrederisUlrich Keller

Abstract

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 and poor prognosis. We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo 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). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]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 [(68)Ga]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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Methods Mentioned

BETA
flow
biopsy
PCR
flow cytometry
xenografts
xenograft
imaging techniques
electrophoresis
imaging technique

Clinical Trials Mentioned

NCT01359657

Software Mentioned

GraphPad Prism
Kaluza® Flow Analysis
CellQuest
SPSS Statistics
Siemens Esoft

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