title: (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma.
abstract: Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand (68)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent (68)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUVmax, SUVmean). Tumor-to-background ratios (TBR) were calculated for both PET probes. (68)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. (68)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUVmean and SUVmax of 3.0±1.5 and 3.9±2.0 respectively. Respective values for (18)F-FET were 4.4±2.0 (SUVmean) and 5.3±2.3 (SUVmax). TBR for SUVmean and SUVmax were higher for (68)Ga-Pentixafor than for (18)F-FET (SUVmean 154.0±90.7 vs. 4.1±1.3; SUVmax 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high (68)Ga-Pentixafor uptake; regions of the same tumor without apparent (68)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, (68)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, (68)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
authors.affiliation: 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany; 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany; 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lückerath
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 3. Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Kleinlein
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 3. Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Camelia Maria
authors.initials: CM
authors.lastname: Monoranu
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 4. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Linsenmann
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 4. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Almuth F
authors.initials: AF
authors.lastname: Kessler
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 3. Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Rudelius
authors.affiliation: 5. Scintomics GmbH, Fürstenfeldbruck, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Kropf
authors.affiliation: 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany; 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 4. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Ralf-Ingo
authors.initials: RI
authors.lastname: Ernestus
authors.affiliation: 6. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.affiliation: 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 4. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Löhr
authors.affiliation: 1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany; 2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany; 7. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
mesh_terms: D000328:Adult; D000368:Aged; D056831:Coordination Complexes / Q000008:administration & dosage*; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D019718:Receptors, CXCR4 / Q000032:analysis*; D014054:Tomography / Q000379:methods*
chemical_list: C000597686:68Ga-pentixafor; C527276:CXCR4 protein, human; D056831:Coordination Complexes; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4
keywords: CXCR4; Glioblastoma; PET.; chemokine receptor; neuro-oncology