Automated no-carrier-added synthesis of [1-11C]-labeled D- and L-enantiomers of lactic acid.
The first purely chemical method for automated no-carrier-added synthesis of [1-(11)C]-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 [(11)C]HCN (trapped as [(11)C]KCN) the intermediate dl-(R,S)-[1-(11)C]-2-hydroxypropanenitrile was prepared. Its rapid acid hydrolysis gave dl-(R,S)-[1-(11)C]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-(11)C]lactic acid enantiomers were separated by chiral ligand-exchange chromatography. Two novel chiral selectors for HPLC enantiomeric separation of alpha-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-(11)C]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 [(11)C]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/micromol.
Drandarov
Konstantin
K
Center for Radiopharmaceutical Sciences, Swiss Federal Institute of Technology Zurich, University Hospital Zürich, CH-8091 Zurich, Switzerland.
Schubiger
P August
PA
Westera
Gerrit
G
D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D019344:Lactic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D011854:Radiochemistry; D013237:Stereoisomerism
D002250:Carbon Radioisotopes; D019344:Lactic Acid