[¹⁸F]AlF-NOTA-FAPI-04: FAP-targeting specificity, biodistribution, and PET/CT imaging of various cancers

In this pilot study, we developed a new tracer, [¹⁸F]AlF-labeled FAPI-04 chelated with NOTA, denoted as [¹⁸F]AlF-NOTA-FAPI-04, and tested the specificity, biodistribution, and clinical application for PET/computed tomography (CT) imaging of various types of cancers in patients.

In vitro binding specificity of FAPI-04 to FAP was verified in U87 cells confocal of a fluorescence-labeled variant. In vivo imaging, competition, and dynamic scanning analyses were conducted to evaluate [¹⁸F]AlF-NOTA-FAPI-04 imaging in xenograft mouse model using small-animal PET/CT. The application of [¹⁸F]AlF-NOTA-FAPI-04 was analyzed by imaging different types of cancers in patients.

Both in vitro and in vivo results showed high binding specificity of FAPI-04 to FAP. High intratumoral uptake and fast body clearance of the tracer were observed in the xenograft mouse model and cancer patients. High-contrast images and negligible radiation exposure to normal tissue were observed on [¹⁸F]AlF-NOTA-FAPI-04 PET/CT in 28 patients with 8 different types of cancers. Five of 28 patients underwent PET/CT scanning at 1 h, 2 h, and 4 h after intravenous injection of [¹⁸F]AlF-NOTA-FAPI-04. Seven patients with advanced lung cancer underwent dual-tracer imaging, and 44 and 37 metastatic lesions were detected by [¹⁸F]AlF-NOTA-FAPI-04 PET/CT and [¹⁸F]F-FDG PET/CT, respectively. Overall, 80.0% of metastatic lesions was identified by both [¹⁸F]AlF-NOTA-FAPI-04 and ¹⁸F-FDG, 17.8% by [¹⁸F]AlF-NOTA-FAPI-04 PET/CT only, and 2.2% by [¹⁸F]FDG PET/CT only.

[¹⁸F]AlF-NOTA-FAPI-04 offers high specificity as a tracer for FAP imaging and allows fast imaging with high contrast in tumors. [¹⁸F]AlF-NOTA-FAPI-04 is better at identifying metastatic lesions in patients with advanced lung cancer than [¹⁸F]FDG, and its use may facilitate tumor staging.