Radiosynthesis and first preclinical evaluation of the novel 11C-labelled FAP inhibitor 11C-FAPI: A comparative study of 11C-FAPIs and [68Ga]Ga-DOTAFAPI-04 in a high–FAP-expression mouse model.

Abstract

Background: 68Ga-labelled fibroblast activation protein inhibitors, such as [68Ga]Ga-DOTA-FAPI-04 and [68Ga]Ga-DOTA-FAPI-46, have been successfully applied in positron emission tomography imaging of various tumour types. To broaden the spectrum of applicable PET tracers for extended imaging studies of FAP-dependent diseases, we herein report the radiosynthesis and preclinical evaluation of two 11C-labelled FAP inhibitors, 11C-FAPI-01 and 11C-FAPI-02. Results: 11C-FAPI-01 and 11C-FAPI-02 were synthesized in over 15% radiochemical yields, with specific activities of 67 GBq/µmol and 34 GBq/µmol, respectively, at the end of synthesis and radiochemical purities greater than 99%. In U87MG tumour xenograft PET studies, the three tracers experienced higher specific uptake at the tumour site. However, because of significant differences in metabolism and clearance, [68Ga]Ga-DOTA-FAPI-04 experienced high uptake in the kidney, whereas 11C-FAPI-01 and 11C-FAPI-02 showed high uptake in the liver and intestine. Biodistribution studies revealed significant hepatobiliary excretion of 11C-FAPI-01 and 11C-FAPI-02. 11C-FAPI-02 showed higher specific tumour uptake in U87MG xenografts (1.71 ± 0.08% injected dose per gram of tissue [ID/g]) than 11C-FAPI-01 (1.34 ± 0.10%ID/g) and [68Ga]Ga-DOTA-FAPI-04 (1.29 ± 0.04%ID/g) after 30 min p.i. In orthotopic glioma models, the uptake values were 0.07 ± 0.03% ([68Ga]Ga-DOTA-FAPI-04) and 0.16 ± 0.03% (11C-FAPI-02), respectively. Conclusion: 11C-FAPI-01 and 11C-FAPI-02 are interesting candidates for translation to the clinic, taking advantage of the shorter half-life and physical imaging properties of C-11. The availability of 11C-FAPI-01 and 11C-FAPI-02 may allow extended PET studies of FAP-related diseases, such as cancer, arthritis, heart diseases, or pulmonary fibrosis.