Supercritical fluid synthesis and on-line preparative supercritical fluid chromatography of 11C-labelled compounds in supercritical ammonia

Abstract

An automated supercritical fluid synthesis (SFS) system, designed for reaction and on-line preparative supercritical fluid chromatography (SFC) of 11C-labelled (t1/2 = 20.3 min) compounds in supercritical ammonia, is described. The synthesis and on-line SFC purification of [methyl-11C]anisole, L-[methyl-11C]methionine and 4-methoxyphenyl[11C]guanidine gave a >98% radiochemically pure product within 30 min. [methyl-11C]Anisole was obtained from reaction of phenol with [11C]methyl iodide and was used as a model reaction to evaluate the synthetic procedure of the system. 4-Methoxyphenyl[11C]guanidine was produced by reaction of p-anisidine with [11C]cyanogen bromide to give the 11C-labelled cyanamide, followed by reaction with ammonia to obtain the 11C-guanidine compound. Both D- and L-[methyl-11C]methionine were produced by reaction of [11C]methyl iodide and D- and L-homocysteine thiolactone hydrochloride, respectively. The effect of base concentration on the radiochemical yield and enantiomeric purity of 11C-methionine was investigated, and it was found that 2.5 equiv. of base gave a radiochemical yield >95% with 2-3% racemization. In a typical synthesis and on-line SFC purification of 11C-methionine, a 5 μA h (45 μA, 6.6 min) bombardment to produce [11C]carbon dioxide gave a 3.1 GBq sterile solution of 11C-methionine. © Acta Chemica Scandinavica 1997.