In vivo molecular imaging of chemokine receptor CXCR 4 expression in patients with advanced multiple myeloma

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 [68Ga]Pentixafor for in vivo mapping of CXCR4 expression d...

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Bibliographic Details
Published in:EMBO molecular medicine 2015-04, Vol.7 (4), p.477-487
Main Authors: Philipp‐Abbrederis, Kathrin, Herrmann, Ken, Knop, Stefan, Schottelius, Margret, Eiber, Matthias, Lückerath, Katharina, Pietschmann, Elke, Habringer, Stefan, Gerngroß, Carlos, Franke, Katharina, Rudelius, Martina, Schirbel, Andreas, Lapa, Constantin, Schwamborn, Kristina, Steidle, Sabine, Hartmann, Elena, Rosenwald, Andreas, Kropf, Saskia, Beer, Ambros J, Peschel, Christian, Einsele, Hermann, Buck, Andreas K, Schwaiger, Markus, Götze, Katharina, Wester, Hans‐Jürgen, Keller, Ulrich
Format: Article
Language:English
Subjects:
Biomarkers
Blood cells
Bone marrow
Cancer therapies
CD34 antigen
Cell adhesion & migration
Chemokines
Computed tomography
CXCR4 protein
Flow cytometry
Kinases
Multiple myeloma
Patients
Positron emission tomography
Standard deviation
Variance analysis
Xenografts
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Summary: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 [68Ga]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). [68Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [68Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [18F]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 [68Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4‐directed therapeutic approaches in MM and other diseases.
ISSN:1757-4676
1757-4684
DOI:10.15252/emmm.201404698