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

We have previously reported that N-(2-[(18)F]fluoropropionyl)-L-methionine ([(18)F]FPMET) selectively accumulates in tumors. However, due to the poor pharmacokinetics of [(18)F]FPMET in vivo, the potential clinical translation of this observation is hampered. In this study, we rationally designed and synthesized [(18)F] or [(11)C]labeled N-position L-glutamic acid analogues for tumor imaging. N-(2-[(18)F]fluoropropionyl)-L-glutamic acid ([(18)F]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 [(18)F]FPGLU was primarily transported through the X(AG) (–) system and was not incorporated into protein. [(18)F]FPGLU was stable in urine, tumor tissues, and blood. We were able to use [(18)F]FPGLU in PET imaging and obtained high tumor to background ratios when visualizing tumors tissues in animal models.