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

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