Experimental study of internal irradiation with a novel targeted FAPI molecular probe for the treatment of human pancreatic cancer xenografts

Abstract Objective: The purpose of this study was to analyze and compare the therapeutic effects of ¹³¹I-FAPI-Y4, ¹³¹I-FAPI-caerin1.1, and ¹³¹I-FAPI-46 on pancreatic cancer cell xenografts. Methods: ① The in vitro antitumor effects of FAPI-Y4, FAPI-caerin 1.1 and FAPI-46 were verified by CCK8 and colony formation assays. ② FAPI-Y4, FAPI-caerin1.1 and FAPI-46 were labeled by a radioiodine demethylation reaction, and their basic properties were determined. The uptake and elution of ¹³¹I-FAPI-Y4, ¹³¹I-FAPI-caerin 1.1 and ¹³¹I-FAPI-46 in human pancreatic cancer cells were studied by cell uptake and elution assays. ③ A PANC-1 nude mouse model was established to compare the efficacy of internal irradiation with that of a novel targeted molecular probe in the treatment of pancreatic cancer.H&E staining was used to detect dead cells in the tumor tissue sections, and immunohistochemical staining was used to analyze the expression of the FAP antibody in the tumor cells. Results: ① In vitro, FAPI-caerin1.1 and FAPI-46 inhibited the proliferation of human pancreatic cancer cells and normal pancreatic ductal epithelial cells in vitro in a concentration-dependent manner, and their inhibitory effects were significantly different (P < 0.05), whereas FAPI-Y4 had no significant inhibitory effect on the proliferation of human pancreatic cancer cells or normal pancreatic ductal epithelial cells in vitro, indicating potential biological safety. ② In vivo experiments revealed that ¹³¹I-labeled FAPI-Y4 had better antitumor activity than ¹³¹I-labeled FAPI-caerin1.1 and FAPI-46. Conclusion: ¹³¹I-labeled FAPI-Y4, FAPI-caerin1.1 and FAPI-46 significantly inhibited the proliferation and growth of PANC-1 cells (P < 0.05), and ¹³¹I-FAPI-Y4 has a more significant therapeutic effect than the other compounds and may be potential therapeutic drugs for human pancreatic cancer.