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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

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.
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1]
  1. Washington Univ., St. Louis, MO (United States)
Publication Date:
Grant/Contract Number:
SC0004832
Type:
Accepted Manuscript
Journal Name:
Journal of Medicinal Chemistry
Additional Journal Information:
Journal Volume: 58; Journal Issue: 9; Journal ID: ISSN 0022-2623
Publisher:
American Chemical Society (ACS)
Research Org:
Washington Univ., St. Louis, MO (United States). School of Medicine
Sponsoring Org:
USDOE Office of Science (SC)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES
OSTI Identifier:
1346033

Bouhlel, Ahlem, Zhou, Dong, Li, Aixiao, Yuan, Liya, Rich, Keith M., and McConathy, Jonathan. 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. United States: N. p., Web. doi:10.1021/jm502023y.
Bouhlel, Ahlem, Zhou, Dong, Li, Aixiao, Yuan, Liya, Rich, Keith M., & McConathy, Jonathan. 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. United States. doi:10.1021/jm502023y.
Bouhlel, Ahlem, Zhou, Dong, Li, Aixiao, Yuan, Liya, Rich, Keith M., and McConathy, Jonathan. 2015. "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". United States. doi:10.1021/jm502023y. https://www.osti.gov/servlets/purl/1346033.
@article{osti_1346033,
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},
author = {Bouhlel, Ahlem and Zhou, Dong and Li, Aixiao and Yuan, Liya and Rich, Keith M. and McConathy, Jonathan},
abstractNote = {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.},
doi = {10.1021/jm502023y},
journal = {Journal of Medicinal Chemistry},
number = 9,
volume = 58,
place = {United States},
year = {2015},
month = {4}
}