No-carrier-added 3-(2'-[18F]fluoroethyl)spiperone, a new dopamine receptor-binding tracer for positron emission tomography.

No-carrier-added (NCA)3-(2'-[18F]fluoroethyl)spiperone (5), a new dopamine receptor-binding radiopharmaceutical for positron emission tomography, was synthesized by two different methods. Alkylation of the amide nitrogen in spiperone by NCA [18F]fluorobromoethane in the presence of a strong base gave 5 (Method A). Experimental methods were also developed for the syntheses of functional 3-N-alkylderivatives of spiperone such as 3-(2'-bromoethyl)- or 3-(2'-methylsulfonyloxyethyl)spiperone (4a and 4b, respectively). These derivatives (4) reacted with NCA Ag18F, Cs18F or K18F/Kryptofix 222 in acetonitrile or DMSO to give 5 (Method B). Method B, using K18F/Kryptofix 222 in acetonitrile provided 5 in multimillicure amounts (30-40% isolated radiochemical yield) with a specific activity of 2-10/mumol (EOS) in less than 60 min. This one-step, one-pot synthesis is simple, and the high radiochemical yield of 5, as well as the 110 min half-life of 18F, permit multiple tomographic studies a day with one preparation. Tomographic results in monkey brain with 5 are consistent with the labeling of dopamine-D2 receptor systems.