[18F]Fluoropyruvate: radiosynthesis and initial biological evaluation

The radiosynthesis of [18F]fluoropyruvate was investigated using numerous precursors were synthesized from ethyl 2,2‐diethoxy‐3‐hydroxypropanoate (5) containing different leaving groups: mesylate, tosylate, triflate, and nonaflate. These precursors were evaluated for [18F]fluoride incorporation with triflate being superior. The subsequent hydrolysis step was investigated, and an acidic hydrolysis was optimized. After establishing suitable purification and formulation methods, the [18F]fluoropyruvate could be isolated in ca. 50% d.c. yield. The [18F]fluoropyruvate was evaluated in vitro for its uptake into tumor cells using adenocarcinomic human alveolar basal epithelial cells (A549) and unfortunately showed an uptake of approximately 0.1% of the applied dose per 100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in vivo using nude mice showed a high degree of bone uptake from defluorination, which will limit its potential as an imaging agent for metabolic processes. Copyright © 2014 John Wiley & Sons, Ltd. Herein, we report on the first successful radiosynthesis of [18F]fluoropyruvate using numerous precursors with the α‐carbonyl group protected as a ketal and containing different sulfonate leaving groups. The hydrolysis step, purification, and formulation methods were investigated and optimized and gave [18F]fluoropyruvate in ca. 50% decay corrected yield. [18F]Fluoropyruvate was evaluated in vitro and in vivo. The biological results are reported.