RAPID METHOD FOR RADIOFLUORINATION OF PYRIDINE DERIVATIVES: PROSTHETIC GROUPS FOR LABELLING BIOACTIVE MOLECULES

摘要

Ethyl 2-[~(18)F]fluoro-4-pyridine and ethyl 6-[~(18)F]fluoro-3-pyridine carboxylates were synthesized by catalyzed nucleophlic no-carrier-added radiofluorination. Treatment of the ethyl-2-(N,N,N-trimethylammonium)-4-pyridine- and ethyl-6-(N,N,N-trimethylammonium)-3-pyridine carboxylate.treflate precursors with radiofluoride and Kryptofix 2.2.2 in anhydrous acetonitrile at 95°C provided these radiofluorinated intermediates with a greater than 90% radiochemical yield within 2 min reaction time. These intermediates served as precursors to obtain the activated N-succinimidyl 2-[~(18)F]fluoro-4-pyridine and 6-[~(18)F]fluoro-3-pyridine carboxylate esters for efficient coupling to amine functions in bioactive molecules. This technique was used to radiofluorinate a model chemotactic peptide (N-Formyl-Nle-Leu-Phe-Nle-Tyr-Lys). Biodistribution studies in normal CBA/J mice revealed very rapid clearance through the renal system.