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

Research Paper

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

Constantin Lapa1,2, Katharina Lückerath1,2, Irene Kleinlein2,3, Camelia Maria Monoranu2,3, Thomas Linsenmann2,4, Almuth F. Kessler2,4, Martina Rudelius2,3, Saskia Kropf5, Andreas K. Buck1,2, Ralf-Ingo Ernestus2,4, Hans-Jürgen Wester6✉, Mario Löhr2,4*, Ken Herrmann1,2,7*

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

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Citation:
Lapa C, Lückerath K, Kleinlein I, Monoranu CM, Linsenmann T, Kessler AF, Rudelius M, Kropf S, Buck AK, Ernestus RI, Wester HJ, Löhr M, Herrmann K. 68Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma. Theranostics 2016; 6(3):428-434. doi:10.7150/thno.13986. Available from https://www.thno.org/v06p0428.htm

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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 (SUVmax, SUVmean). 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 SUVmean and SUVmax of 3.0±1.5 and 3.9±2.0 respectively. Respective values for 18F-FET were 4.4±2.0 (SUVmean) and 5.3±2.3 (SUVmax). TBR for SUVmean and SUVmax were higher for 68Ga-Pentixafor than for 18F-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 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.