Radiosynthesis and Biological Evaluation of N-[18F]Labeled Glutamic Acid as a Tumor Metabolic Imaging Tracer

We have previously reported that N-(2-[F-18]fluoropropionyl)-L-methionine ([F-18]FPMET) selectively accumulates in tumors. However, due to the poor pharmacokinetics of [F-18]FPMET in vivo, the potential clinical translation of this observation is hampered. In this study, we rationally designed and synthesized [F-18] or [C-11]labeled N-position L-glutamic acid analogues for tumor imaging. N-(2-[F-18]fluoropropionyl)-L-glutamic acid ([F-18]FPGLU) was synthesized with a 30 +/- 10% (n = 10, decay-corrected) overall radiochemical yield and a specific activity of 40 +/- 25 GBq/mu mol (n = 10) after 130 min of radiosynthesis. In vitro cell experiments showed that [F-18]FPGLU was primarily transported through the X-AG system and was not incorporated into protein. [F-18]FPGLU was stable in urine, tumor tissues, and blood. We were able to use [F-18]FPGLU in PET imaging and obtained high tumor to background ratios when visualizing tumors tissues in animal models.