title: Improved synthesis of N-succinimidyl 4-[18F]fluorobenzoate and its application to the labeling of a monoclonal antibody fragment.
abstract: Our previously reported method for the 18F labeling of antibodies using N-succinimidyl 4-[18F]fluorobenzoate (SFB) involved a rather long synthesis time. Here we present an improved method for the synthesis of SFB which reduces the synthesis time by about 45 min. A reaction time of 5-8 min (versus 25 min for the original procedure) was sufficient in the fluorination step to form 4-[18F]fluorobenzaldehyde in high yield. In the original method, 30-35 min was necessary to convert 4-[18F]fluorobenzoic acid to SFB using dicyclohexylcarbodiimide and N-hydroxysuccinimide. When N,N'-disuccinimidyl carbonate was used, facile conversion of 4-fluorobenzoic acid to SFB was seen at a micromolar level. At a tracer level, no product was formed at room temperature; however, complete consumption of starting material was observed. Heating at 150 degrees C resulted in the formation of SFB in more than 80% yield in 1-3 min. HPLC purification of SFB was necessary since use of crude SFB, or SFB purified using a silica solid-phase cartridge column, resulted in lower protein coupling yields. Furthermore, use of crude SFB resulted in cross-linking and lower immunoreactivity of antibody. Largely as a result of the considerable reduction in total labeling time, these modifications have increased the amount of 18F-labeled antibody available per 100 mCi of [18F]fluoride by 30-35%.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: G
authors.initials: G
authors.lastname: Vaidyanathan
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D001565:Benzoates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry; D007202:Indicators and Reagents; D007553:Isotope Labeling; D051379:Mice; D013056:Spectrophotometry, Ultraviolet; D013388:Succinimides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D000911:Antibodies, Monoclonal; D001565:Benzoates; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D013388:Succinimides; C075713:N-succinimidyl-4-fluorobenzoate