Direct ¹⁸F-Labeling of Biomolecules via Spontaneous Site-Specific Nucleophilic Substitution by F^– on Phosphonate Prostheses

Abstract

We describe a high radiochemical yield late-stage direct 18F-labeling of bare biomolecules containing common active groups. Spontaneity and site-selectivity are attributed to the remarkably higher rates of nucleophilic substitution reactions on phosphonates than on other electrophiles by F– at various hydrogen bond forms. Rapid access to many medicinally significant 18F-labeled biomolecules is achieved at 21–68% radiochemical yields and 35.9–55.1 GBq μmol–1 molar activities both manually or automatically.