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