[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

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.

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