Preclinical evaluation and pilot clinical study of 18FAlF-labeled FAPI-tracer for PET imaging of cancer associated fibroblasts

In recent years, fibroblast activation protein (FAP) has emerged as an attractive target for the diagnosis and radiotherapy of cancers using FAP-specific radioligands. Herein, we aimed to design a novel 18F-labeled FAP tracer (18FAlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The 18FAlF-P-FAPI novel tracer was prepared in an automated manner within 42 min with a non-decay corrected radiochemical yield of 32 ± 6% (n = 8). Among A549-FAP cells, 18FAlF-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer 18FFAPI-42, 18FAlF-P-FAPI exhibited lower levels of cellular efflux in the A549-FAP cells and higher stability in vivo. Micro-PET imaging in the A549-FAP tumor model indicated higher specific tumor uptake of 18FAlF-P-FAPI (7.0 ± 1.0% ID/g) compared to patent tracers 18FFAPI-42 (3.2 ± 0.6% ID/g) and 68GaGa-FAPI-04 (2.7 ± 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, 18FAlF-P-FAPI and 18FFDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that 18FAlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies.