title: Optimization of the solid-phase synthesis of [18F] radiolabeled peptides for positron emission tomography.
abstract: Establishing improved methods for the radiolabeling of peptides with fluorine-18 via solid-phase peptide synthesis (SPPS) is desirable for the efficient synthesis of peptide-based molecular imaging agents. This work focuses on the development of a standardized platform to facilitate the reliable and efficient synthesis of high-purity fluorine-18 radiolabeled peptides for in vivo imaging with positron emission tomography (PET). Seven commercially available resins were selected for solid-phase radiolabeling of the model peptide VQAAIDYING with 4-[(18)F]fluorobenzoic acid ([(18)F]FBA). A wide range of radiochemical yields (18.8 ± 1.5% to 41.2 ± 5.3%) was obtained using standard conditions (coupling: 3 eq amino acid, 3 eq HATU, 6 eq DIPEA, 1.5 h, r.t.; cleavage: 94% TFA, 3 h, r.t.). After modification of coupling reagents and employing heated reactions to 37°C, radiochemical yields were improved by as much as 35.3% over standard conditions. When the optimized conditions were applied to the synthesis of [(18)F]FBA-PEG(28)-A20FMDV2, which targets the α(v)β(6) integrin in vivo, radiochemical yields improved by as much as 73.4% over those obtained using standard coupling and cleavage conditions. This platform can be utilized to improve the synthesis of peptide-based molecular probes for molecular imaging with PET.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: White
authors.forename: Sven H
authors.initials: SH
authors.lastname: Hausner
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carpenter
authors.forename: Julie L
authors.initials: JL
authors.lastname: Sutcliffe
mesh_terms: D005462:Fluorine Radioisotopes; D007553:Isotope Labeling / Q000379:methods*; D009842:Oligopeptides / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D060327:Solid-Phase Synthesis Techniques / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D019275:Radiopharmaceuticals