[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

  • Oncotarget. 2017 Sep 16;8(56):95606-95619. doi: 10.18632/oncotarget.21024.
Sarah M Schwarzenböck  1 ,  Jan Stenzel  2 ,  Thomas Otto  1 ,  Heike V Helldorff  1 ,  Carina Bergner  1 ,  Jens Kurth  1 ,  Stefan Polei  2 ,  Tobias Lindner  2 ,  Romina Rauer  2 ,  Alexander Hohn  1 ,  Oliver W Hakenberg  3 ,  Hans J Wester  4 ,  Brigitte Vollmar  5 ,  Bernd J Krause  1
Affiliations
  • 1. Department of Nuclear Medicine, Rostock University Medical Centre, 18057 Rostock, Germany.
  • 2. Core Facility Small Animal Imaging, Rostock University Medical Centre, 18057 Rostock, Germany.
  • 3. Department of Urology, Rostock University Medical Centre, 18057 Rostock, Germany.
  • 4. Institute for Radiopharmaceutical Chemistry, Technische Universität München, 85748 Garching, Germany.
  • 5. Institute for Experimental Surgery, Rostock University Medical Centre, 18057 Rostock, Germany.
PMID: 29221153 DOI: 10.18632/oncotarget.21024
Abstract

Purpose: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords
CXCR4; MRI; [68Ga]Pentixafor; prostate cancer; small animal PET/CT.
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