Purpose: Tryptophan is metabolized mainly via kynurenine and serotonin pathways. Kynurenine pathway plays a role in neurodegenerative disease and verity of cancer. Based on the mechanism of tryptophan metabolism, 18F-labeled tryptophan may be an ideal PET tracer for imaging kynurenine pathway where L-5-[18F]fluorotryptophan (L-5-[18F]FTrp) would not undergo serotonin pathway. 5-[18F]fluorotryptophan was synthesized as a racemic mixture via Balz-Schiemann reaction.1 Recently, L-5-[18F]FTrp and D-5-[18F]FTrp were synthesized via a Cu-catalyzed radiofluorodeboronylation2 with low radiochemical yield of 1.5% and synthesis time of 193±46 min. In this work, we report an improved method for the synthesis of L-5-[18F]FTrp with high radiochemical yield and optical purity. Methods: The precursor was prepared via Miyaura-Ishiyama-Hartwig borylation starting from N-Boc-L-5-bromotryptophan tert-butyl ester. L-5-[18F]FTrp was synthesized via a reported butanol-enhanced Cu-catalyzed nucleophilic [18F]fluorination3 at 110 °C for 15 min. followed by hydrolysis using 6 N HCl at 110 °C for 10 min. The radiotracer was purified by a semi-preparative HPLC using Phenomenex Luna C18 column (5 μ, 250 x 10 mm). The radiochemical purity and enantiopurity of the synthesized radiotracer were determined by HPLC using Astec Chirobiotic T chiral column (5 μm, 250 x 4.6 mm). Results: L-5-[18F]FTrp was synthesized with decay-corrected radiochemical yield of 42% and total synthesis time of 60 min under the optimized condition. Both of the radiochemical purity and optical purity of the L-5-[18F]FTrp were higher than 99%. Conclusions: We have synthesized L-5-[18F]FTrp using one-pot two-step procedure in good radiochemical yield, high radiochemical purity and high optical purity. Evaluation of this radiotracer in animal models, and study of its metabolism are under way.

In situ radiosynthesis of L-5-[18F]fluorotryptophan

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.