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

作者：Kaixuan Li, Alexa L. Gilberti, Jocelyn A. Marden, Hari K. Akula, Alyssa C. Pollard, Shuwen Guo, Bao Hu, Peter J. Tonge, Wenchao Qü · 发表于：Journal of Medicinal Chemistry · 年份：2024 · DOI：10.1021/acs.jmedchem.4c00774 · 被引用次数：6 · 研究领域：Amino Acid Enzymes and Metabolism、Epigenetics and DNA Methylation、Radiopharmaceutical Chemistry and Applications

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.