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

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

doi:10.1021/jm502023y

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 · Mon Apr 06 00:00:00 EDT 2015 · Journal of Medicinal Chemistry

DOI:https://doi.org/10.1021/jm502023y· OSTI ID:1346033

Bouhlel, Ahlem ^[1]; Zhou, Dong ^[2]; Li, Aixiao ^[2]; Yuan, Liya ^[2]; Rich, Keith M. ^[2]; McConathy, Jonathan ^[2]

Washington Univ., St. Louis, MO (United States); Office of Scientific and Technical Information (OSTI)
Washington Univ., St. Louis, MO (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Washington Univ. School of Medicine, St. Louis, MO (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: SC0004832

OSTI ID:: 1346033

Journal Information:: Journal of Medicinal Chemistry, Journal Name: Journal of Medicinal Chemistry Journal Issue: 9 Vol. 58; ISSN 0022-2623

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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A silicon-labelled amino acid suitable for late-stage fluorination and unexpected oxidative cleavage reactions in the preparation of a key intermediate in the Strecker synthesis Scroggie, Kymberley R.; Alcock, Lisa J.; Matos, Maria J. Peptide Science, Vol. 110, Issue 3 https://doi.org/10.1002/pep2.24069	journal	April 2018
A silicon-labelled amino acid suitable for late-stage fluorination and unexpected oxidative cleavage reactions in the preparation of a key intermediate in the Strecker synthesis Scroggie, Kr; Alcock, Lj; Matos, Mj Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.23629	text	January 2018

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