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.