Radiosynthesis of N.C.A. Sodium [18F]Fluoroacetate and Radiopharmacological Characterization in Rats and Tumor-Xenografted Mice

S.      Richter; R.      Bergmann; J.      Pietzsch; B.      Beuthien-Baumann; F.      Wuest

Abstract

A convenient remotely-controlled synthesis of no-carrier-added sodium [18F]fluoroacetate is described. Three ethyl esters 1a- 1c and three t-butyl esters 3a-3c containing either a methanesulfonyloxy- (OMs), p-toluenesulfonyloxy- (OTs) or p-nitrobenzenesulfonyloxy (ONs) leaving group were investigated as labeling precursors. The optimized radiosynthesis of n.c.a. sodium [18F]fluoroacetate was performed in two steps: (1) Incorporation of fluorine into (methanesulfonyloxy)-acetic acid t-butyl ester 3a as the superior labeling precursor in CH3CN at 100 ° C for 5 min followed by (2) acidic hydrolysis of the resulting [18F]fluoroacetic acid t-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 tumor-bearing mice in comparison with [11C]acetate.

Keywords: 18F-labelling, [18F]fluoroacetate, positron emission tomography (PET)