Design and implementation of an automated DT-PhotoFluor radiosynthesis module for 18F-fluorination of aliphatic, branched chain amino acids

Abstract

Herein we report the automation and scale-up of a photofluorination process key to the production of branched-chain aliphatic radiotracers such as (S)-5-[¹⁸F]fluorohomoleucine ((S)-5-[¹⁸F]]FHL). (S)-5-[¹⁸F]FHL is a leucine analogue that is primarily taken up by the L-type amino acid transporter (LAT or System L). LAT1 expression levels correlate closely with tumor proliferation, angiogenesis, and treatment outcomes, making it an attractive target for molecular imaging of cancer. We have previously synthesized (S)-5-[¹⁸F]FHL and tested this tracer in mice bearing PC3 (prostate) or U87 (glioma) xenografts in order to establish its feasibility for detecting and monitoring treatment for a broad range of cancers. In this study, the radiosynthesis of 5-[¹⁸F]FHL is demonstrated on an automated DT-PhotoFluor module with a radiochemical yield of 20.1 ± 4.8% (n = 3), radiochemical purity of 94.5 ± 4.9% (n = 3), and a synthesis time of ~ 75 min. The reported DT-PhotoFluor module will allow for higher molar activity, better reproducibility, and reduced radiation exposure for upcoming first-in-human studies.