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

PURPOSE: The aim was to characterize the properties of [(68)Ga]Pentixafor as tracer for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and to investigate its correlation with [(18)F]FDG PET/CT, magnetic resonance imaging (MRI) and ex vivo analyses. METHODS: Static [(68)Ga]Pentixafor and [(18)F]FDG PET as well as morphological/ diffusion weighted MRI and (1)H 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 [(68)Ga]Pentixafor was significantly lower compared to [(18)F]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 [(68)Ga]Pentixafor tumor uptake and ex vivo receptor expression. Spectroscopy showed typical spectra of prostate cancer. CONCLUSION: PC-3 tumor uptake of [(68)Ga]Pentixafor was existent but lower compared to [(18)F]FDG. No significant correlation of ex vivo tumor CXCR4 receptor expression and [(68)Ga]Pentixafor tumor uptake was shown. CXCR4 receptor expression on the surface of PC-3 cells was existent but rather low possibly explaining the limited [(68)Ga]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 [(68)Ga]Pentixafor in prostate cancer imaging.