Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.
An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min.
Department of Biomedical Imaging, Genentech Research and Early Development, Genentech Inc., South San Francisco, California, USA.
Herman S
HS
Gill
Jan
J
Marik
D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*
D000480:Alkynes; D001386:Azides; D005462:Fluorine Radioisotopes; D010455:Peptides; D003300:Copper