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

Abstract

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.

Editorial for Special Issue: The Chorioallantoic Membrane (CAM) Model—Traditional and State-of-the Art Applications: The 1st International CAM Conference

“…Moreover, the pre-labeling of tumor cells allowed for longitudinal bioluminescence imaging. In another study, it was reported that radiotracers specifically accumulate in the ovografts and can be followed in the CAM model using positron emission tomography and magnetic resonance scanning [7]. Moreover, the specific target-binding of radiopharmaceuticals was assessed in MRI using specific blocking agents [8].…”

The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

“…More recently, 18 F-siPSMA-14 PET/MRI was used to image PSMA-positive and -negative tumors both in ovo and in vivo 23 . 68 Ga-Pentixafor PET/MRI has also been used to evaluate colorectal cancer uptake and blocking with a CXCR4 antagonist in addition to 18 F-FDG, which was used as a viability marker 24 . Current unresolved limitations with this model relate to variable tumor growth rates, difficulties cannulating the CAM vessels for dynamic imaging, and the need to cool the egg to immobilize the embryo, which negatively impacts radiotracer delivery, internalization, and metabolism 23 .…”