Synthesis and evaluation of 2-amino-4-[(18)F]fluoro-2-methylbutanoic acid (FAMB): relationship of amino acid transport to tumor imaging properties of branched fluorinated amino acids.

Radiolabeled amino acids represent a promising class of tumor imaging agents, and the determination of the optimal characteristics of these tracers remains an area of active investigation. A new (18)F-labeled branched amino acid, 2-amino-4-[(18)F]fluoro-2-methylbutanoic acid (FAMB), has been prepared in 36% decay-corrected yield using no-carrier-added [(18)F]fluoride. In vitro uptake assays with rat 9L gliosarcoma cells suggest that [(18)F]FAMB was transported primarily via the L type amino acid transport system.

Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection.

syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC, 16 and 17), analogues of anti-1-amino-3-[18F]fluorocyclobutyl-1-carboxylic acid (FACBC), were prepared to evaluate the contributions of C-3 substitution and configuration on the uptake of these radiolabeled amino acids in a rodent model of brain tumors. Radiofluorinated targets [18F]16 and [18F]17 were prepared by no-carrier-added radiofluorination from their corresponding methanesulfonyl esters 12 and 13, respectively, with decay-corrected radiochemical yields of 30% for [18F]16 and 20% for [18F]17. In amino acid transport assays performed in vitro using 9L gliosarcoma cells, both [18F]16 and [18F]17 were substrates for L type amino acid transport, while [18F]17 but not [18F]16 was a substrate for A type transport.

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.

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.