title: Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET).
abstract: Two [(18)F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[(18)F]fluoro-2-methylheptanoic acid ((S)-[(18)F]FAMHep, (S)-[(18)F]14) and (S)-2-amino-7-[(18)F]fluoroheptanoic acid ((S)-[(18)F]FAHep, (S)-[(18)F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[(18)F]15 but not (S)-[(18)F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[(18)F]15 in normal brain. (S)-[(18)F]15 had imaging properties similar to those of (S)-[(18)F]FET in the DBT tumor model while (S)-[(18)F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging.
authors.affiliation: Department of Radiology, School of Medicine, Washington University in St. Louis , St. Louis, Missouri 63110, United States.|Inserm, Vascular Center of Marseille (UMR_S1076), CERIMED, Aix-Marseille University , Marseille, France.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Bouhlel
authors.affiliation: Doisy College of Health Sciences, Saint Louis University , St. Louis, Missouri 63103, United States.
authors.forename: Wadha
authors.initials: W
authors.lastname: Alyami
authors.affiliation: Department of Radiology, School of Medicine, Washington University in St. Louis , St. Louis, Missouri 63110, United States.
authors.forename: Aixiao
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, School of Medicine, Washington University in St. Louis , St. Louis, Missouri 63130, United States.
authors.forename: Liya
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, School of Medicine, Washington University in St. Louis , St. Louis, Missouri 63130, United States.
authors.forename: Keith
authors.initials: K
authors.lastname: Rich
authors.affiliation: Department of Radiology, School of Medicine, Washington University in St. Louis , St. Louis, Missouri 63110, United States.|Department of Radiology, University of Alabama at Birmingham , Birmingham, Alabama 35249, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
mesh_terms: D019943:Amino Acid Substitution; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D021542:Amino Acids, Neutral / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry*; D008297:Male; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: C000611073:2-amino-7-fluoro-2-methylheptanoic acid; D000596:Amino Acids; D021542:Amino Acids, Neutral; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D014443:Tyrosine; D006859:Hydrogen