Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[F-18]fluoro-2-methylpentanoic Acid ((R)-, (S)-[F-18]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors

摘要

A novel F-18-labeled alpha,alpha-disubstituted amino acid-based tracer, 2-amino-5-[F-18]fluoro-2-methylpentanoic acid ([F-18]FAMPe), has been developed for brain tumor imaging with a longer alkyl side chain than previously reported compounds to increase brain availability via system L amino acid transport. Both enantiomers of [F-18]FAMPe were obtained in good radiochemical yield (24-52% n = 8) and high radiochemical purity (>99%). In vitro uptake assays in mouse DBT gliomas cells revealed that (S)-[F-18]FAMPe enters cells partly via sodium-independent system L transporters and also Via other nonsystem A transport systems including transporters that recognize glutamine. Biodistribution and small animal PET/CT studies in the mouse DBT model of glioblastoma showed that both (R)- and,(S)-[F-18]FAMPe have good tumor imaging properties with the (S)-enantiomer providing higher tumor uptake and tumor to brain ratios. Comparison of the SUVs showed that (S)-[F-18]FAMPe had higher tumor to brain ratios compared to (S)-[F-18]FET, a well-established system L substrate.