title: 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.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Bouhlel
authors.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Aixiao
authors.initials: A
authors.lastname: Li
authors.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Liya
authors.initials: L
authors.lastname: Yuan
authors.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Rich
authors.affiliation: †Department of Radiology, and ‡Department of Neurosurgery, Washington University in Saint Louis, School of Medicine, St. Louis, Missouri 63110, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D021542:Amino Acids, Neutral / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D010421:Pentanoic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: C000599952:2-amino-5-fluoro-2-methylpentanoic acid; D026921:Amino Acid Transport Systems, Neutral; D000597:Amino Acids, Branched-Chain; D021542:Amino Acids, Neutral; D005462:Fluorine Radioisotopes; D010421:Pentanoic Acids; D019275:Radiopharmaceuticals
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