CAM-Xenograft Model Provides Preclinical Evidence for the Applicability of [⁶⁸Ga]Ga-Pentixafor in CRC Imaging

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Increased expression of CXCR4 has been associated with liver metastasis, disease progression, and shortened survival. Using in vitro cell binding studies and the in ovo model, we aimed to investigate the potential of [⁶⁸Ga]Ga-Pentixafor, a radiotracer specifically targeting human CXCR4, for CRC imaging. Specific membrane binding and internalisation of [⁶⁸Ga]Ga-Pentixafor was shown for HT29 cells, but not for HCT116 cells. Accordingly, [⁶⁸Ga]Ga-Pentixafor accumulated specifically in CAM-xenografts derived from HT29 cells, but not in HCT116 xenografts, as determined by µPET/MRI. The CAM-grown xenografts were histologically characterised, demonstrating vascularisation of the graft, preserved expression of human CXCR4, and viability of the tumour cells within the grafts. In vivo viability was further confirmed by µPET/MRI measurements using 2-[¹⁸F]FDG as a surrogate for glucose metabolism. [⁶⁸Ga]Ga-Pentixafor µPET/MRI scans showed distinct radiotracer accumulation in the chick embryonal heart, liver, and kidneys, whereas 2-[¹⁸F]FDG uptake was predominantly found in the kidneys and joints of the chick embryos. Our findings suggest that [⁶⁸Ga]Ga-Pentixafor is an interesting novel radiotracer for CRC imaging that is worth further investigation. Moreover, this study further supports the suitability of the CAM-xenograft model for the initial preclinical evaluation of targeted radiopharmaceuticals.