PREPARATION OF A POTENTIAL POSITRON EMISSION TOMOGRAPHIC RADIOLIGAND FOR THE DOPAMINE TRANSPORTER

NNC 12-0722 is(4-fluorophenyl)methoxy)-methoxy)ethyl]-4-methyl piperaz ine) is a new selective inhibitor of the dopamine transporter. [C-11]N NC 120722 was prepared by N-methylation of the desmethyl compound with [C-11]methyl iodide. The total radio-chemical yield of [C-11]NNC 12-0 722 was 40%-50% with an overall synthesis time of 30-35 min. The radio -chemical purity was higher than 99% and the specific radioactivity ab out 1500 Ci/mmol (55 GBq/mumol). Autoradiographic examination of [C-11 ]NNC 12-0722 binding on whole hemisphere cryosections from human brain post mortem demonstrated specific binding in the caudate nucleus and putamen. In a positron emission tomographic examination of [C-11]NNC 1 2-0722 in a cynomolgus monkey there was a rapid uptake of radioactivit y in the brain. In the striatum, a region with a high density of dopam ine transporters, the radioactivity was two times higher than in the c erebellum. These results indicate that [C-11]NNC 12-0722 may be a usef ul radioligand for labelling of the dopamine transporter in man.