In vivo molecular imaging of chemokine receptor CXCR4 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 [(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.
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.
Kathrin
K
Philipp-Abbrederis
Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany ulrich.keller@lrz.tum.de Herrmann_K1@ukw.de.
Ken
K
Herrmann
Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
Stefan
S
Knop
Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
Margret
M
Schottelius
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
Matthias
M
Eiber
Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Katharina
K
Lückerath
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.
Elke
E
Pietschmann
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stefan
S
Habringer
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
Carlos
C
Gerngroß
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.
Katharina
K
Franke
Institute of Pathology, Universitätsklinikum Würzburg and CCC Mainfranken, Würzburg, Germany.
Martina
M
Rudelius
Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Andreas
A
Schirbel
Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Constantin
C
Lapa
Institute of Pathology, Technischen Universität München, Munich, Germany.
Kristina
K
Schwamborn
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.
Sabine
S
Steidle
Institute of Pathology, Universitätsklinikum Würzburg and CCC Mainfranken, Würzburg, Germany.
Elena
E
Hartmann
Institute of Pathology, Universitätsklinikum Würzburg and CCC Mainfranken, Würzburg, Germany.
Andreas
A
Rosenwald
Scintomics GmbH, Fürstenfeldbruck, Germany.
Saskia
S
Kropf
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
Ambros J
AJ
Beer
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Christian
C
Peschel
Department of Internal Medicine II, Division of Hematology and Medical Oncology, Universitätsklinikum Würzburg, Würzburg, Germany.
Hermann
H
Einsele
Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany.
Andreas K
AK
Buck
Department of Nuclear Medicine, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Markus
M
Schwaiger
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katharina
K
Götze
Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany Scintomics GmbH, Fürstenfeldbruck, Germany.
Hans-Jürgen
HJ
Wester
III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany ulrich.keller@lrz.tum.de Herrmann_K1@ukw.de.
Ulrich
U
Keller
D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D057054:Molecular Imaging / Q000379:methods*; D015335:Molecular Probes / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods*; D019718:Receptors, CXCR4 / Q000096:biosynthesis*
C527276:CXCR4 protein, human; D015335:Molecular Probes; D009363:Neoplasm Proteins; D019718:Receptors, CXCR4
CXCR4; chemokine receptor; in vivo imaging; multiple myeloma; positron emission tomography