Simplified and robust one-step radiosynthesis of [18 F]DCFPyL via direct radiofluorination and cartridge-based purification

Abstract

[¹⁸ F]DCFPyL is a clinical-stage PET radiotracer used to image prostate cancer. This report details the efficient production of [¹⁸ F]DCFPyL using single-step direct radiofluorination, without the use of carboxylic acid-protecting groups. Radiolabeling reaction optimization studies revealed an inverse correlation between the amount of precursor used and the radiochemical yield. This simplified approach enabled automated preparation of [¹⁸ F]DCFPyL within 28 minutes using HPLC purification (26% ± 6%, at EOS, n = 4), which was then scaled up for large-batch production to generate 1.46 ± 0.23 Ci of [¹⁸ F]DCFPyL at EOS (n = 7) in high molar activity (37 933 ± 4158 mCi/μmol, 1403 ± 153 GBq/μmol, at EOS, n = 7). Further, this work enabled the development of [¹⁸ F]DCFPyL production in 21 minutes using an easy cartridge-based purification (25% ± 9% radiochemical yield, at EOS, n = 3).

Keywords: HPLC-free purification; PET imaging of prostate cancer; automated production; prostate-specific membrane antigen (PSMA) ligand; protection-free radiolabeling.