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

An automated supercritical fluid synthesis (SFS) system, designed for reaction and on-line preparative supercritical fluid chromatography (SFC) of C-11-labelled (t(1/2) = 20.3 min) compounds in supercritical ammonia, is described. The synthesis and on-line SFC purification of [methyl-C-11]anisole, L-[methyl-C-11]methionine and 4-methoxyphenyl[C-11]guanidine gave a >98% radiochemically pure product within 30 min. [methyl-C-11]Anisole was obtained from reaction of phenol with [C-11]methyl iodide and was used as a model reaction to evaluate the synthetic procedure of the system. 4-Methoxyphenyl[C-11]guanidine was produced by reaction of p-anisidine with [C-11]cyanogen bromide to give the C-11-labelled cyanamide, followed by reaction with ammonia to obtain the C-11-guanidine compound. Both D- and L-[methyl-C-11]methionine were produced by reaction of [C-11]methyl iodide and D- and L-homocysteine thiolactone hydrochloride, respectively. The effect of base concentration on the radiochemical yield and enantiomeric purity of C-11-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 C-11-methionine, a 5 mu A h (45 mu A, 6.6 min) bombardment to produce [C-11]carbon dioxide gave a 3.1 GBq sterile solution of C-11-methionine.