Synthesis, Radiolabeling, and Biological Evaluation of (R)- and (S)-2-Amino-5-[(18)F]fluoro-2-methylpentanoic Acid ((R)-, (S)-[(18)F]FAMPe) as Potential Positron Emission Tomography Tracers for Brain Tumors.

Academic Article

Abstract

  • 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.
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    Keywords

  • Amino Acid Transport Systems, Neutral, Amino Acids, Branched-Chain, Amino Acids, Neutral, Animals, Brain, Brain Neoplasms, Fluorine Radioisotopes, Glioma, Male, Mice, Inbred BALB C, Pentanoic Acids, Positron-Emission Tomography, Radiopharmaceuticals, Stereoisomerism, Tissue Distribution
  • Digital Object Identifier (doi)

    Author List

  • Bouhlel A; Zhou D; Li A; Yuan L; Rich KM; McConathy J
  • Start Page

  • 3817
  • End Page

  • 3829
  • Volume

  • 58
  • Issue

  • 9