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 18F-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-[18F]fluoroalanine (l-[18F]FAla), using a serine-derivatized, five-membered-ring sulfamidate
as the radiofluorination precursor. A deuterated analogue, l-3-[18F]fluoroalanine-d3 (l-[18F]FAla-d3), was also prepared to improve metabolic
stability. Both l-[18F]FAla and l-[18F]FAla-d3 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-[18F]FAla, l-[18F]FAla-d3, and the d-enantiomer, d-[18F]FAla-d3,
to image tumors was evaluated in U87MG tumor-bearing mice. Despite
the significant bone uptake was observed for both l-[18F]FAla and l-[18F]FAla-d3,
the latter had enhanced tumor uptake compared to l-[18F]FAla, and d-[18F]FAla-d3 was not specifically taken up by the tumors. The enhanced tumor
uptake of l-[18F]FAla-d3 compared with
its nondeuterated counterpart, l-[18F]FAla, warranted
the further biological investigation of this radiotracer as a potential
cancer imaging agent.