Production of L-[1-11C]valine by HPLC resolution.

Based on a recently developed analytical technique, preparative high-performance liquid chromatographic (HPLC) resolution of DL-[1-11C]valine has been achieved. A conventional reverse-phase HPLC column and a chiral mobile phase (aqueous solution of L-proline, cupric acetate, and sodium acetate) were used. The copper can be removed from the L-valine fraction by precipitation as the sulfide, and final purification by cation-exchange chromatography yields L-[1-11C]valine in a form that is acceptable for clinical positron tomographic studies. This purification method does not remove the L-proline introduced in the resolution process, but added L-proline did not affect the tissue distribution of L-[1-14C]valine in rats. We have produced up to 60 mCi of L-[1-11C]valine in an overall synthesis and resolution time of 50 min. This procedure should be adaptable to the rapid resolution of other C-11-labeled amino acid racemates.