Preclinical evaluation and pilot clinical study of [18F ]AlF-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 18 Flabeled FAP tracer ([F-18]AlF-P-FAPI) for FAP imaging and evaluated its potential for clinical application. The [F-18]AlF-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, [F-18]A1F-P-FAPI demonstrated specific uptake, rapid internalization, and low cellular efflux. Compared to the patent tracer [F-18]FAPI-42, [F-18] AlF-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 [F-18]AlF-P-FAPI (7.0 +/- 1.0% ID/g) compared to patent tracers [F-18]FAPI-42 (3.2 +/- 0.6% ID/g) and [Ga-68]Ga-FAPI-04 (2.7 +/- 0.5% ID/g). Furthermore, in an initial diagnostic application in a patient with nasopharyngeal cancer, [F-18]AlF-P-FAPI and [F-18]FDG PET/CT showed comparable results for both primary tumors and lymph node metastases. These results suggest that [F-18]AlF-P-FAPI can be conveniently prepared, with promising characteristics in the preclinical evaluation. The feasibility of FAP imaging was demonstrated using PET studies. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.