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Title: 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

Journal Article · · Journal of Medicinal Chemistry
DOI:https://doi.org/10.1021/jm502023y· OSTI ID:1346033
 [1];  [1];  [1];  [1];  [1];  [1]
  1. Washington Univ., St. Louis, MO (United States)
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In this paper, 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. Finally, 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.

Research Organization:
Washington Univ., St. Louis, MO (United States). School of Medicine
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0004832
OSTI ID:
1346033
Journal Information:
Journal of Medicinal Chemistry, Vol. 58, Issue 9; ISSN 0022-2623
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

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