title: Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid.
abstract: Novel radiopharmaceuticals, including amino acids, that target neoplasms through their altered metabolic states have shown promising results in preclinical and clinical studies. Two fluorinated analogues of alpha-aminoisobutyric acid, 2-amino-3-fluoro-2-methylpropanoic acid (FAMP) and 3-fluoro-2-methyl-2-(methylamino)propanoic acid (N-MeFAMP), have been radiolabeled with fluorine-18, characterized in amino acid uptake assays, and evaluated in vivo in normal rats and a rodent tumor model. The key steps in the syntheses of both radiotracers involved the preparation of cyclic sulfamidate precursors. Radiosyntheses of both [18F]FAMP and [18F]N-MeFAMP via no-carrier-added nucleophilic substitution provided high yields (>78% decay-corrected) in high radiochemical purity (>99%). Amino acid transport assays using 9L gliosarcoma cells demonstrated that both compounds are substrates for the A type amino acid transport system, with [18F]N-MeFAMP showing higher specificity than [18F]FAMP for A type transport. Tissue distribution studies in normal Fischer rats and Fischer rats implanted intracranially with 9L gliosarcoma tumor cells were also performed. At 60 min postinjection, the tumor vs normal brain ratio of radioactivity was 36:1 in animals receiving [18F]FAMP and 104:1 in animals receiving [18F]N-MeFAMP. On the basis of these studies, both [18F]FAMP and [18F]N-MeFAMP are promising imaging agents for the detection of intracranial neoplasms via positron emission tomography.
authors.affiliation: Department of Radiology at Emory University Hospital, School of Medicine, 1364 Clifton Road Northeast, Atlanta, Georgia 30322, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: McConathy
authors.forename: Laurent
authors.initials: L
authors.lastname: Martarello
authors.forename: Eugene J
authors.initials: EJ
authors.lastname: Malveaux
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Camp
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Simpson
authors.forename: Chiab P
authors.initials: CP
authors.lastname: Simpson
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Bowers
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
authors.forename: Mark M
authors.initials: MM
authors.lastname: Goodman
mesh_terms: D026924:Amino Acid Transport System A / Q000037:antagonists & inhibitors / Q000378:metabolism; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000621:Aminoisobutyric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D005462:Fluorine Radioisotopes; D018316:Gliosarcoma / Q000378:metabolism; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D009368:Neoplasm Transplantation; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured
chemical_list: C455819:2-amino-3-fluoro-2-methylpropanoic acid; C455820:3-fluoro-2-methyl-2-(methylaminio)propanoic acid; D026924:Amino Acid Transport System A; D000596:Amino Acids; D000621:Aminoisobutyric Acids; D005462:Fluorine Radioisotopes; D008024:Ligands; D011422:Propionates; D019275:Radiopharmaceuticals