THE F-18 LABELED ALKYLATING AGENT 2,2,2-TRIFLUOROETHYL TRIFLATE - SYNTHESIS AND SPECIFIC ACTIVITY

A method for synthesizing the alkylating agent 2,2,2-trifluoroethyl tr iflate labelled with [F-18]fluoride in the two position is presented. Ethyl [2-F-18]-trifluoroacetate was synthesized by the nucleophilic re action of [F-18]F with ethyl bromodifluoroacetate in DMSO (45-60%, 5 m in, 80 degrees C) and subsequently converted to [2-F-18]-2,2,2-trifluo roethanol using alane in THF (85-95%, 2 min, 40 degrees C). Reaction w ith triflic anhydride in 2,6-lutidine produced [2-F-18]-2,2,2-trifluor oethyl triflate (70-80%, 1 min, 0 degrees). In all three cases the pro duct was removed from the reaction vessel by heating to distil under a stream of nitrogen. [2-F-18]-2,2,2-Trifluoroethyl triflate was used t o label 2-oxoquazepam by N-alkylation in a toluene:DMF mixture (80-85% , 20 min, 120 degrees C). Although no-carrier-added [F-18]F- was used, considerable unlabelled ethyl trifluoroacetate was produced in the fi rst reaction. Varying the conditions for the fluoro-debromination reac tion did not appreciably improve the relative ratio of labelled to unl abelled ester. The specific activity of the labelled 1,4-benzodiazepin e-2-one obtained from 1850 MBq [F-18]F- was found to be approximate to 37 MBq/mu mol (1 mCi/mu mol).