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.

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.

• Authors: Ahlem Bouhlel, Dong Zhou, Aixiao Li, Liya Yuan, Keith M Rich, Jonathan McConathy
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 58 Issue 9 Pg. 3817-29 (May 14 2015) ISSN: 1520-4804 [Electronic] United States
• PMID: 25843369 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 2-amino-5-fluoro-2-methylpentanoic acid
• Amino Acid Transport Systems, Neutral
• Amino Acids, Branched-Chain
• Amino Acids, Neutral
• Fluorine Radioisotopes
• Pentanoic Acids
• Radiopharmaceuticals

Topics

• Amino Acid Transport Systems, Neutral (metabolism)
• Amino Acids, Branched-Chain (chemical synthesis, chemistry, pharmacology)
• Amino Acids, Neutral (chemical synthesis, chemistry, pharmacology)
• Animals
• Brain (diagnostic imaging, metabolism)
• Brain Neoplasms (diagnostic imaging, metabolism)
• Fluorine Radioisotopes
• Glioma (diagnostic imaging, metabolism)
• Male
• Mice, Inbred BALB C
• Pentanoic Acids (chemical synthesis, chemistry, pharmacokinetics)
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Stereoisomerism
• Tissue Distribution