Open AccessSynthesis, 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(s) -
Ahlem Bouhlel,
Dong Zhou,
Aixiao Li,
Yuan Lu,
Keith M. Rich,
Jonathan McConathy
Publication year - 2015
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/jm502023y
Subject(s) - chemistry , biodistribution , amino acid , enantiomer , amino acid transporter , transporter , glutamine , in vitro , in vivo , tumor cells , radiochemistry , stereochemistry , biochemistry , cancer research , gene , biology , microbiology and biotechnology
A novel (18)F-labeled α,α-disubstituted amino acid-based tracer, 2-amino-5-[(18)F]fluoro-2-methylpentanoic acid ([(18)F]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 [(18)F]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)-[(18)F]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)-[(18)F]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)-[(18)F]FAMPe had higher tumor to brain ratios compared to (S)-[(18)F]FET, a well-established system L substrate.