Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-5-[¹⁸F]fluoro-2-methylpentanoic acid ((R)-, (S)-[¹⁸F]FAMPe) as potential positron emission tomography tracers for brain tumors

A novel ¹⁸F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[¹⁸F]fluoro-2-methylpentanoic acid ([¹⁸F]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 [¹⁸F]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)-[¹⁸F]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)-[¹⁸F]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)-[¹⁸F]FAMPe had higher tumor to brain ratios compared to (S)-[¹⁸F]FET, a well-established system L substrate.