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

Ahlem Bouhlel, Dong Zhou, Aixiao Li, Liya Yuan, Keith M. Rich, Jonathan McConathy

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3817-3829
Number of pages13
JournalJournal of Medicinal Chemistry
Volume58
Issue number9
DOIs
StatePublished - May 14 2015

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this