Labeling proteins with fluorine-18 using N-succinimidyl 4-[18F]fluorobenzoate.
Two methods were investigated for the no-carrier-added synthesis of N-succinimidyl 4-[18F]fluorobenzoate (S[18F]FB). The first, an attempted nucleophilic aromatic substitution by [18F]fluoride on N-succinimidyl 4-nitrobenzoate was unsuccessful. The second method involved three steps; [18F]fluoride for trimethylammonium substitution on 4-formyl-N,N,N-trimethylanilinium triflate, oxidation to 4-[18F]fluorobenzoic acid, followed by reaction with N-hydroxysuccinimide and dicyclohexylcarbodiimide to form S[18F]FB. Total synthesis and purification time was 100 min and the overall radiochemical yield was 25% (decay corrected). A monoclonal antibody F(ab')2 fragment could be labeled in 40-60% yield by reaction with S[18F]FB for 15-20 min. The tissue distribution in normal mice and in vitro tumor binding of the antibody F(ab')2 labeled by reaction with S[18F]FB were comparable to those observed for the fragment after radioiodination using N-succinimidyl 4-[125I]iodobenzoate.
Vaidyanathan
G
G
Department of Radiology, Duke University Medical Center, Durham, NC 27710.
Zalutsky
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001565:Benzoates / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes; D006207:Half-Life; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000378:metabolism; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000737:chemistry*; D013388:Succinimides / Q000138:chemical synthesis*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D001565:Benzoates; D005462:Fluorine Radioisotopes; D007128:Immunoglobulin Fragments; D011506:Proteins; D013388:Succinimides; C075713:N-succinimidyl-4-fluorobenzoate