Radiosynthesis of n.c.a. sodium [¹⁸F]fluoroacetate and radiopharmacological characterization in rats and tumour-xenografted mice

A convenient remotely-controlled synthesis of no-carrier-added sodium [18F]fluoroacetate is described. Three ethyl esters 1a-1c and three tert.-butyl esters 3a-3c containing either a methanesulfonyloxy- (OMs), p-toluenesulfonyloxy- (OTs) or p-nitrobenzenesulfonyloxy (ONs) leaving group were investigated as labelling precursors. The optimized radiosynthesis of n.c.a. sodium [18F]fluoroacetate was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid tert.-butyl ester 3a as the superior labelling precursor in acetonitrile at 100°C for 5 min followed by (2) acidic hydrolysis of the resulting [18F]fluoroacetic acid tert.-butyl ester at 100°C for 10 min to afford [18F]fluoroacetic acid. Several consecutive purification steps using anion exchange cartridges (Alltech Maxi-Clean SAX) and Sep-Pak neutral alumina cartridges gave sodium [18F]fluoroacetate in reproducible radiochemical yields of 20-25% (decay-corrected, n=20) in high radiochemical purity (>99%) within 50 min. Radiopharmacological characterization of sodium [18F]fluoroacetate was studied in Wistar rats and HT-29 tumour-bearing mice in comparison with [11C]acetate.