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 F-18-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 F-18-labeled biomolecules is achieved at 21-68% radiochemical yields and 35.9-55.1 GBq mu mol(-1) molar activities both manually or automatically.

Automated summary

This method achieves high radiochemical yield late-stage direct F-18 labeling of bare biomolecules containing common active groups, with spontaneity and site-selectivity attributed to higher rates of nucleophilic substitution reactions on phosphonates. Rapid access to many medicinally significant F-18-labeled biomolecules is achieved manually or automatically with high radiochemical yields and molar activities.