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

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.