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-18-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-18]fluoroalanine (l-[F-18]FAla), using a serine-derivatized, five-membered-ring sulfamidate as the radiofluorination precursor. A deuterated analogue, l-3-[F-18]fluoroalanine-d(3) (l-[F-18]FAla-d(3)), was also prepared to improve metabolic stability. Both l-[F-18]FAla and l-[F-18]FAla-d(3) 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-18]FAla, l-[F-18]FAla-d(3), and the d-enantiomer, d-[F-18]FAla-d(3), to image tumors was evaluated in U87MG tumor-bearing mice. Despite the significant bone uptake was observed for both l-[F-18]FAla and l-[F-18]FAla-d(3), the latter had enhanced tumor uptake compared to l-[F-18]FAla, and d-[F-18]FAla-d(3) was not specifically taken up by the tumors. The enhanced tumor uptake of l-[F-18]FAla-d(3) compared with its nondeuterated counterpart, l-[F-18]FAla, warranted the further biological investigation of this radiotracer as a potential cancer imaging agent.