Performance evaluation of 18F-FAPI-74 in the FAP expressing pancreatic cancer: preclinical comparison study with 68Ga-FAPI-04

1492 Purpose: Fibroblast activation protein (FAP), a protein promoting tumor growth and progression, is overexpressed in cancer associated fibroblasts but has low expression in normal organs. In the previous study, we demonstrated the diagnostic and therapeutic utility of 64Cu/68Ga-FAP inhibitor (FAPI)-04 PET and 225Ac-FAPI-04 in mice (Watabe T, et al. J Nucl. Med. 2020). In this study, we have successfully synthesized 18F-FAPI-74 and evaluated the biodistribution and performance of 18F-FAPI-74 in human pancreatic cancer xenografts. Methods: Male nude mice (n=9) were injected with human pancreatic cancer cells (PANC-1) three weeks before the PET scan. Two xenograft mice were investigated after the intravenous injection of 18F-FAPI-74 (14.0 ± 1.4 MBq) by 70 min-dynamic PET scan. Static scans 1 hour after injection of 18F-FAPI-74 (12.0 ± 1.6 MBq) were acquired for the other seven xenograft mice. The uptakes were compared with our previous study using 68Ga-FAPI-04. Immunohistochemical staining with FAP antibody was also performed to confirm FAP expression in the PANC-1 xenograft after PET study. Results: Dynamic imaging showed a fast clearance through kidneys and a slow washout in the tumors. Static imaging showed mild uptake in the tumors and relatively high uptake in the intestine, bone and gallbladder. Tracer uptake in the tumor was higher in 18F-FAPI-74 PET than 68Ga-FAPI-04 PET (1 hour post-injection). Immunohistochemical staining showed abundant expression of FAP in the PANC-1 xenograft. Conclusions: This study showed the feasibility of 18F-FAPI-74 for the diagnosis of FAP-expressing pancreatic cancer. 18F-FAPI-74 showed higher uptake in the tumor xenograft model with FAP expression than 68Ga-FAPI-04, suggesting the advantage of higher detection rate as well as wide availability of 18F compared to 68Ga.Figure 1.18F-FAPI-74 PET imaging (1 hour post-injection) in PANC-1 xenograft model.Figure 2. Tracer uptake in the tumor and normal organs on 18F-FAPI-74 PET.Figure 3. Comparison of tracer uptake in the tumor and normal organs between 18F-FAPI-74 and 68Ga-FAPI-04 PET. (*p