Preparation of a potential positron emission tomographic radioligand for the dopamine transporter.
NNC 12-0722 (1-[2-(bis(4-fluorophenyl)-methoxy)ethyl]-4-methyl piperazine) is a new selective inhibitor of the dopamine transporter. [11C]NNC 12-0722 was prepared by N-methylation of the desmethyl compound with [11C]methyl iodide. The total radiochemical yield of [11C]NNC 12-0722 was 40%-50% with an overall synthesis time of 30-35 min. The radiochemical purity was higher than 99% and the specific radioactivity about 1500 Ci/mmol (55 GBq/mumol). Autoradiographic examination of [11C]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 [11C]NNC 12-0722 in a cynomolgus monkey there was a rapid uptake of radioactivity in the brain. In the striatum, a region with a high density of dopamine transporters, the radioactivity was two times higher than in the cerebellum. These results indicate that [11C]NNC 12-0722 may be a useful radioligand for labelling of the dopamine transporter in man.
Müller
L
L
Department of Psychiatry and Psychology, Karolinska Hospital, Stockholm, Sweden.
Halldin
C
C
Foged
C
C
Karlsson
P
P
Hall
H
H
Swahn
C G
CG
Suzdak
P D
PD
Hohlweg
R
R
Nielsen
E B
EB
Farde
L
L
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002352:Carrier Proteins / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis*; D051381:Rats; D014055:Tomography, Emission-Computed
D002352:Carrier Proteins; C086871:NNC 12-0722; D009419:Nerve Tissue Proteins; D010879:Piperazines; D004298:Dopamine