Automated radiochemical synthesis of [18F]FBEM: a thiol reactive synthon for radiofluorination of peptides and proteins.
The automated radiochemical synthesis of N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM, IUPAC name: N-maleoylethyl-4-[(18)F]fluorobenzamide), a prosthetic group for radiolabeling the free sulfhydryl groups of peptides and proteins, is herein described. 4-[(18)F]fluorobenzoic acid was first prepared by nucleophilic displacement of a trimethylammonium moiety on a pentamethylbenzyl benzoate ester with [(18)F]fluoride. In the second step the ester was cleaved under acidic conditions. Finally, 4-[(18)F]fluorobenzoic acid was coupled to N-(2-aminoethyl)maleimide using diethylcyanophosphate and diisopropylethyl amine. Following high-performance liquid chromatography (HPLC) purification, [(18)F]FBEM was obtained in 17.3±7.1% yield (not decay corrected) in approximately 95 min. Isolation from the HPLC eluate and preparation for subsequent use, which was conducted manually, required an additional 10-15 min. The measured specific activity for three batches was 181.3, 251.6, and 351.5 GBq/μmol at the end of bombardment (EOB).
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Building 10, Room 1C401, MSC 1180, Bethesda, MD 20892, USA. dk7k@nih.gov
Dale O
DO
Kiesewetter
Orit
O
Jacobson
Lixin
L
Lang
Xiaoyuan
X
Chen
D057205:Automation, Laboratory; D002851:Chromatography, High Pressure Liquid; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D008301:Maleimides / Q000138:chemical synthesis*; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
D005462:Fluorine Radioisotopes; D008301:Maleimides; C512447:N-(2-(4-18F-fluorobenzamido)ethyl)maleimide; D010455:Peptides; D011506:Proteins; D019275:Radiopharmaceuticals