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

EMBO Molecular Medicine

Kathrin Philipp-Abbrederis⁶  Ken Herrmann³  Stefan Knop¹  Margret Schottelius⁵  Matthias Eiber⁴  Katharina Lückerath³  Elke Pietschmann⁶  Stefan Habringer⁶  Carlos Gerngroß⁴  Katharina Franke⁶  Martina Rudelius²  Andreas Schirbel³  Constantin Lapa³  Kristina Schwamborn⁷  Sabine Steidle⁶  Elena Hartmann²  Andreas Rosenwald²  Saskia Kropf⁸  Ambros J Beer⁴  Christian Peschel⁶  Hermann Einsele¹  Andreas K Buck³  Markus Schwaiger⁴  Katharina Götze⁶  Hans-Jürgen Wester⁵ 

[1] Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany;Institute of Pathology, Universitätsklinikum Würzburg and CCC Mainfranken, Würzburg, Germany;Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany;Department of Nuclear Medicine, Technische Universität München, Munich, Germany;Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany;III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany;Institute of Pathology, Technischen Universität München, Munich, Germany;Scintomics GmbH, Fürstenfeldbruck, Germany

关键词: chemokine receptor;    CXCR4;    in vivo imaging;    multiple myeloma;    positron emission tomography;   

DOI  :  10.15252/emmm.201404698

来源: Wiley

【 摘 要 】

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 [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.

Synopsis

The CXCR4 PET tracer Pentixafor is a novel tool for in vivo imaging of multiple myeloma to help stratify patients for CXCR4-directed drugs and also a potential carrier for radionuclides or drugs to target the cancer cells and their microenvironment.

• Chemokine receptor CXCR4 expression impacts cancer dissemination and prognosis.
• [⁶⁸Ga]Pentixafor PET allows in vivo visualization of CXCR4 status in multiple myeloma.
• [⁶⁸Ga]Pentixafor PET could help to select patients for CXCR4-directed treatment (theranostics).

【 授权许可】

CC BY   
© 2015 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.