Simple and rapid radiosynthesis of N-18F-labeled glutamic acid as a hepatocellular carcinoma PET tracer

Abstract

IntroductionWe have reported that N-(2-18F-fluoropropionyl)-L-glutamate (18F-FPGLU) showed good tumor-to-background contrast and 18F-FPGLU was prepared via complex multi-step reaction sequence; here, it is synthesized by a facile two-step reaction sequence. The objectives of this study are to synthesize 18F-FPGLU via a two-step reaction sequence and to evaluate the value of 18F-FPGLU in nude mice bearing human hepatocellular carcinoma SMCC-7721 (HCC SMCC-7721). Methods18F-FPGLU was synthetized from the precursor (2S)-dimethyl 2-(2-bromopropanamido)pentanedioate via the two-step on-column hydrolysis using a modified commercial FDG synthesizer. To investigate the transport mechanism of 18F-FPGLU, we conducted a series of competitive inhibition experiments on HCC SMCC-7721 cells in the absence or presence of Na+ and various types of inhibitors. Small-animal PET–CT imaging was performed on tumor-bearing nude mice using 18F-FPGLU and 2-18F-2-deoxy-D-glucose (18F-FDG). ResultsThe radiochemical yield of 18F-FPGLU was up to 15±5% (EOS, n=10) in 35min with the two-step procedure and the radiochemical purity was higher than 95% with a specific activity of 30–40GBq/μmol. In vitro cell experiments show that 18F-FPGLU is primarily transported through the Na+-dependent system XAG− and Na+-independent system XC−. PET imaging in a tumor model indicates that 18F-FPGLU may be superior to 18F-FDG for hepatocellular carcinoma (HCC) imaging. ConclusionAn optimized route to prepare 18F-FPGLU was developed and 18F-FPGLU was synthetized from the precursor ((2S)-dimethyl 2-(2-bromopropanamido)pentanedioate) via the two-step on-column hydrolysis. 18F-FPGLU was a potential novel PET tracer for HCC imaging.