Synthesis of omega-[18F]fluoroalkyl analogs of YM-09151-2 for the measurement of D2-dopamine receptors with PET.
Two [18F]fluoroalkyl analogs of a neuroleptic YM-09151-2 were synthesized via nucleophilic [18F]fluorination of methanesulfonyloxy- or p-toluenesulfonyloxyalkyl derivatives using no-carrier-added [18F]fluoride. Although 3-[18F]fluoropropylaminobenzamide was obtained in good yield, the yield of 2-[18F]fluoroethyl derivative was severalfold lower. The product, N-[(2RS,3RS)-1-benzyl-2-methylpyrrolidin-3-yl]-5- chloro-2-methoxy-4-(3-[18F]fluoropropyl)-aminobenzamide, was shown to have a striatum-to-cerebellum ratio comparable to that of 11C labeled YM-09151-2 and thus to be a good candidate for measuring D2-receptors in vivo.
Hatano
K
K
Division of Radiopharmaceutical Chemistry, School of Medicine, Tohoku University, Sendai, Japan.
Ido
T
T
Ishiwata
K
K
Hatazawa
J
J
Itoh
M
M
Kawashima
K
K
Iwata
R
R
D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging*; D001923:Brain Chemistry; D005462:Fluorine Radioisotopes; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis*; D017448:Receptors, Dopamine D2; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D001549:Benzamides; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C030265:nemonapride