Automated no-carrier-added synthesis of [1- 11C]-labeled d- and l-enantiomers of lactic acid

Abstract

The first purely chemical method for automated no-carrier-added synthesis of [1- 11C]-labeled d( R)- and l( S)-2-hydroxypropanoic acid (lactic acid) was developed for experimental neurophysiology studies and position emission tomography (PET) diagnosis. Starting from sodium 1-hydroxyethanesulfonate and [ 11C]HCN (trapped as [ 11C]KCN) the intermediate dl-( R,S)-[1- 11C]-2-hydroxypropanenitrile was prepared. Its rapid acid hydrolysis gave dl-( R,S)-[1- 11C]lactic acid, which was isolated by preparative reversed phase HPLC and automatically injected on a second preparative C 18 HPLC column coated with a chiral selector, where both [1- 11C]lactic acid enantiomers were separated by chiral ligand-exchange chromatography. Two novel chiral selectors for HPLC enantiomeric separation of α-hydroxy acids, namely d( R)- or l( S)-2-amino-3-methyl-3-(5-phenylpentylsulfanyl)-butanoic acid were utilized for the preparative HPLC separation of the [1- 11C]lactic acid enantiomers. The preparation of the selectors and the coating procedure for the manufacturing of the preparative chiral HPLC columns are described. A highly efficient trap for [ 11C]HCN is presented. The whole radiosynthesis is automated, takes about 45 min and leads to more than 80% decay corrected overall radiochemical yield of each enantiomer (up to 2.5 GBq) with over 99% radiochemical, chemical and enantiomeric purity. The specific activity at the end of the synthesis is about 400 GBq/μmol.