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

Constantin Lapa, Katharina Lückerath, Irene Kleinlein, Camelia Maria Monoranu, Thomas Linsenmann, Almuth F Kessler, Martina Rudelius, Saskia Kropf, Andreas K Buck, Ralf-Ingo Ernestus, Hans-Jürgen Wester, Mario Löhr, Ken Herrmann, Constantin Lapa, Katharina Lückerath, Irene Kleinlein, Camelia Maria Monoranu, Thomas Linsenmann, Almuth F Kessler, Martina Rudelius, Saskia Kropf, Andreas K Buck, Ralf-Ingo Ernestus, Hans-Jürgen Wester, Mario Löhr, Ken Herrmann

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.

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

Conflict of interest statement

Conflicts of interest: SKr is CEO of Scintomics. HJW is founder and shareholder of Scintomics. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Example of dis- and concordant distribution of 68Ga-Pentixafor and 18F-FET in glioblastoma patients. Given are transaxial slices of contrast-enhanced, T1-weighted MRI, 68Ga-Pentixafor- and 18F-FET-PET in two patients with glioblastoma. Whereas tracer distribution is concordant in patient #14, marked differences can be observed in patient #11.
Figure 2
Figure 2
CXCR4 Expression in CXCR4+ and CXCR4- tumor samples (as assessed by 68Ga-Pentixafor-PET). Exemplary depiction of immunohistochemical staining for CXCR4 in biopsies from both 68Ga-Pentixafor negative (red dotted line; positive in 18F-FET-PET) and positive (green) tumor areas, respectively (patient #1). 68Ga-Pentixafor-PET/CT and T1-weighted rapid three-dimensional gradient-echo technique (MP-RAGE) MR images were transferred to a neuronavigation system for specific sampling. Nuclei are stained with H&E. Magnification: 200x.

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