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Theranostics 2016; 6(3):428-434. doi:10.7150/thno.13986 This issue Cite

Research Paper

⁶⁸Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma

Constantin Lapa^1,2, Katharina Lückerath^1,2, Irene Kleinlein^2,3, Camelia Maria Monoranu^2,3, Thomas Linsenmann^2,4, Almuth F. Kessler^2,4, Martina Rudelius^2,3, Saskia Kropf⁵, Andreas K. Buck^1,2, Ralf-Ingo Ernestus^2,4, Hans-Jürgen Wester^6✉, Mario Löhr^2,4*, Ken Herrmann^1,2,7*

1. Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany
2. Comprehensive Cancer Center Mainfranken, Würzburg, Germany
3. Institute of Pathology, University of Würzburg, Würzburg, Germany
4. Department of Neurosurgery, University Hospital Würzburg, Würzburg, Germany
5. Scintomics GmbH, Fürstenfeldbruck, Germany
6. Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany
7. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, USA
^* Equal contribution

✉ Corresponding author: h.j.westerde

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 ⁶⁸Ga-Pentixafor.

15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent ⁶⁸Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV_max, SUV_mean). Tumor-to-background ratios (TBR) were calculated for both PET probes. ⁶⁸Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.

⁶⁸Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV_mean and SUV_max of 3.0±1.5 and 3.9±2.0 respectively. Respective values for ¹⁸F-FET were 4.4±2.0 (SUV_mean) and 5.3±2.3 (SUV_max). TBR for SUV_mean and SUV_max were higher for ⁶⁸Ga-Pentixafor than for ¹⁸F-FET (SUV_mean 154.0±90.7 vs. 4.1±1.3; SUV_max 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high ⁶⁸Ga-Pentixafor uptake; regions of the same tumor without apparent ⁶⁸Ga-Pentixafor uptake showed no or low receptor expression.

In this pilot study, ⁶⁸Ga-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, ⁶⁸Ga-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.

Keywords: Glioblastoma, neuro-oncology, chemokine receptor, CXCR4, PET.

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