SYNTHESIS OF THE ENANTIOMERS OF [N-METHYL-C-11]PK-11195 AND COMPARISON OF THEIR BEHAVIORS AS RADIOLIGANDS FOR PK BINDING-SITES IN RATS

The enantiomers of [N-methyl-C-11]PK 11195, a radioligand for PET stud ies of PK (peripheral benzodiazepine) binding sites, have been prepare d from the newly synthesized N-desmethyl-enantiomers by C-11-methylati on with N.C.A. [C-11]iodomethane. The brain uptake and retention of ea ch enantiomer was compared with that of the racemic radioligand after i.v. administration into normal rats and into rats with focal cortical lesions. No significant differences in the uptakes of the enantiomers were observed in regions devoid of PK binding sites. However, the R-e nantiomer was retained to a significantly greater extent than the S-en antiomer in olfactory bulbs-tubercles, which contain some PK binding s ites, and also in 9-day-old focal cortical lesions, which are greatly enriched in PK binding sites associated with macrophage infiltration. The observed differences are consistent with the approximately 2-fold greater affinity of the R-enantiomer for PK binding sites reported in vitro and imply that the use of this enantiomer would have advantages over the use of the racemate currently used for PET studies.