Carbon-11 labelling of eticlopride in two different positions--a selective high-affinity ligand for the study of dopamine D-2 receptors using PET.
A new highly selective high-affinity dopamine D-2 receptor antagonist, eticlopride ((-)-(S)-5-chloro-3-ethyl-N-((1-ethyl-2-pyrrolidinyl) methyl)-6-methoxysalicylamide), was labelled with 11C in two different positions ([N-ethyl-11C]eticlopride (I)) and ([methyl-11C]eticlopride (II)). Product I was prepared by N-alkylation of the N-desethyl compound with [11C]ethyl iodide. II was prepared by O-alkylation of the diphenolic precursor with [11C]methyl iodide followed by separation of the two methylated products. The radiochemical yields were 15-20% (EOB) with an overall synthesis time of 45-60 min. Both compounds were isolated by semi-preparative HPLC and the radiochemical purity was in both cases greater than 99%. I was injected i.v. in a Cynomolgus monkey and brain radioactivity was measured by positron emission tomography (PET). The specific activity was 70 Ci/mmol at time of injection. There was a marked accumulation of radioactivity in the basal ganglia, regions known to have a high density of dopamine D-2 receptors.
Halldin
C
C
Karolinska Pharmacy, Stockholm, Sweden.
Farde
L
L
Högberg
T
T
Hall
H
H
Sedvall
G
G
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008252:Macaca fascicularis; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C045989:eticlopride