Biodistribution and Radiation Dosimetry of [18F]AlF-NSFBP4 in Cancer Patients: First-in-Human Study.

Abstract

This first-in-human study aimed to evaluate the radiation dosimetry and target specificity of [18F]AlF-NSFBP4, a novel heterodimeric PET tracer targeting both fibroblast activation protein (FAP) and sodium-dependent multivitamin transporter (SMVT). Eight patients with 5 different cancer types underwent intravenous [18F]AlF-NSFBP4 administration, with dynamic whole-body PET/CT at 5, 15, 30, 60 and 120 minutes. Seven patients additionally underwent [18F]FDG PET/CT for comparison. Time-activity curves per organ were determined. The mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. FAP and SMVT expression were evaluated by immunohistochemical staining. The tracer accumulated in tumors rapidly, with the tumor-to-background ratio (TBR) increasing over time. The average SUVmax and TBR of [18F]AlF-NSFBP4 were higher than the corresponding values of 2-[18F]FDG, while the differences were not statistically significant. Higher tracer uptake in tumors correlated with higher levels of both FAP and SMVT protein expression. The estimated effective dose was 1.82E-02 mSv/MBq. [18F]AlF-NSFBP4 shows strong clinical potential, characterized by excellent tumor visualization and a suitable radiation dose for clinical use.