Synthesis of [18F]2-deoxy-2-fluoro-D-glucose from highly reactive [18F]tetraethylammonium fluoride prepared by hydrolysis of [18F]fluorotrimethylsilane.
18F-Labeled fluorotrimethylsilane was prepared by nucleophilic substitution of chlorotrimethylsilane with reactor produced [18F]fluoride. Hydrolysis of fluorotrimethylsilane by aqueous tetraethylammonium hydroxide followed by removal of water with a mechanical pump gave a powerful source of no carrier added nucleophilic 18F. Reaction of this purified 18F preparation with 4,6-benzylidene-1-beta-O-methyl D-mannopyranoside-2.3-cyclic sulfate was complete in 2 min at 80 degrees C and gave two labeled products with similar retention times on reverse phase HPLC. Allowing for decay and handling losses during deprotection, the maximum yield of [18F]2-deoxy-2-fluoro-D-glucose from no-carrier added tetraethylammonium fluoride was 50%. Incorporation of 18F into organic products was 30% complete in 10 min at room temperature. An identical time-course was observed for reaction of 3-O-triflyl-1,2-5,6-diisopropylidene-D-allofuranose, the starting material for 3-deoxy-3-fluoro-D-glucose. Reaction of tetraethylammonium fluoride with chlorotrimethylsilane was more rapid and much more tolerant of water than the fluorosugar reactions. Chlorotrimethylsilane can be used to recover unreacted 18F from reaction mixtures.
D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D003837:Deoxy Sugars / Q000138:chemical synthesis*; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D005461:Fluorine; D019788:Fluorodeoxyglucose F18; D006868:Hydrolysis; D007553:Isotope Labeling; D007700:Kinetics; D011868:Radioisotopes; D012825:Silicon / Q000138:chemical synthesis*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds; D014297:Trimethylsilyl Compounds / Q000138:chemical synthesis*
D003837:Deoxy Sugars; D011868:Radioisotopes; D013757:Tetraethylammonium Compounds; D014297:Trimethylsilyl Compounds; D019788:Fluorodeoxyglucose F18; D005461:Fluorine; C038077:trimethylfluorosilane; D019789:Tetraethylammonium; D003847:Deoxyglucose; D012825:Silicon