Synthesis and Biological Evaluation of Fluorine-18 and Deuterium Labeled l-Fluoroalanines as Positron Emission Tomography Imaging Agents for Cancer Detection.

To fully explore the potential of F-labeled l-fluoroalanine for imaging cancer and other chronic diseases, a simple and mild radiosynthesis method has been established to produce optically pure l-3-[F]fluoroalanine (l-[F]FAla), using a serine-derivatized, five-membered-ring sulfamidate as the radiofluorination precursor. A deuterated analogue, l-3-[F]fluoroalanine-d (l-[F]FAla-d), was also prepared to improve metabolic stability. Both l-[F]FAla and l-[F]FAla-d were rapidly taken up by 9L/lacZ, MIA PaCa-2, and U87MG cells and were shown to be substrates for the alanine-serine-cysteine (ASC) amino acid transporter. The ability of l-[F]FAla, l-[F]FAla-d, and the d-enantiomer, d-[F]FAla-d, to image tumors was evaluated in U87MG tumor-bearing mice. Despite the significant bone uptake was observed for both l-[F]FAla and l-[F]FAla-d, the latter had enhanced tumor uptake compared to l-[F]FAla, and d-[F]FAla-d was not specifically taken up by the tumors. The enhanced tumor uptake of l-[F]FAla-d compared with its nondeuterated counterpart, l-[F]FAla, warranted the further biological investigation of this radiotracer as a potential cancer imaging agent.