[68Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model - comparison with [18F]FDG PET/CT, MRI and ex vivo receptor expression

The aim was to characterize the properties of [68Ga]Pentixafor as tracer for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and to investigate its correlation with [18F]FDG PET/CT, magnetic resonance imaging (MRI) and ex vivo analyses.

Static [68Ga]Pentixafor and [18F]FDG PET as well as morphological/ diffusion weighted MRI and 1H MR spectroscopy was performed. Imaging data were correlated with ex vivo biodistribution and CXCR4 expression in PC-3 tumors (immunohistochemistry (IHC), mRNA analysis). Flow cytometry was performed for evaluation of localization of CXCR4 receptors (in vitro PC-3 cell experiments).

Tumor uptake of [68Ga]Pentixafor was significantly lower compared to [18F]FDG. Ex vivo CXCR4 mRNA expression of tumors was shown by PCR. Only faint tumor CXCR4 expression was shown by IHC (immuno reactive score of 3). Accordingly, flow cytometry of PC-3 cells revealed only a faint signal, cell membrane permeabilisation showed a slight signal increase. There was no significant correlation of [68Ga]Pentixafor tumor uptake and ex vivo receptor expression. Spectroscopy showed typical spectra of prostate cancer.

PC-3 tumor uptake of [68Ga]Pentixafor was existent but lower compared to [18F]FDG. No significant correlation of ex vivo tumor CXCR4 receptor expression and [68Ga]Pentixafor tumor uptake was shown. CXCR4 receptor expression on the surface of PC-3 cells was existent but rather low possibly explaining the limited [68Ga]Pentixafor tumor uptake; receptor localization in the interior of PC-3 cells is presumable as shown by cell membrane permeabilisation. Further studies are necessary to define the role of [68Ga]Pentixafor in prostate cancer imaging.

Oncotarget. 2017 Sep 16*** epublish ***

Sarah M Schwarzenböck, Jan Stenzel, Thomas Otto, Heike V Helldorff, Carina Bergner, Jens Kurth, Stefan Polei, Tobias Lindner, Romina Rauer, Alexander Hohn, Oliver W Hakenberg, Hans J Wester, Brigitte Vollmar, Bernd J Krause

Department of Nuclear Medicine, Rostock University Medical Centre, 18057 Rostock, Germany., Core Facility Small Animal Imaging, Rostock University Medical Centre, 18057 Rostock, Germany., Department of Urology, Rostock University Medical Centre, 18057 Rostock, Germany., Institute for Radiopharmaceutical Chemistry, Technische Universität München, 85748 Garching, Germany., Institute for Experimental Surgery, Rostock University Medical Centre, 18057 Rostock, Germany.

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