3-(2'-[18F]fluoroethyl)spiperone, a potent dopamine antagonist: synthesis, structural analysis and in-vivo utilization in humans.
The synthesis of 3-(2'-[18F]fluoroethyl)spiperone (1c), a radiotracer useful for imaging the brain dopamine receptor system in vivo using positron emission tomography, is described. Precursors of 1c, the functional 3-N-alkyl derivatives of spiperone (4), were prepared by the alkylation of the amide group in spiperone (2a) by 1,2-disubstituted ethanes under phase transfer conditions. A comprehensive evaluation of the reaction of the derivatives 4a-h with no-carrier-added K18F/Kryptofix clearly indicated that the ketalized derivatives 4e-h were the choice of the precursors for 1c. The i.r., MS and NMR spectral data suggested that under phase transfer reaction conditions, the amide nitrogen was preferentially alkylated. To provide a firm basis for comparison with related analogues, an x-ray analysis was performed on a single crystal of 3-(2'-fluoroethyl)spiperone (1d). The tomographic behavior of 1c in human brain tissue was measured for more than 7 h and was consistent with the labeling of dopamine D-2 receptors.
Satyamurthy
N
N
Department of Radiological Sciences, UCLA School of Medicine 90024.
Barrio
J R
JR
Bida
G T
GT
Huang
S C
SC
Mazziotta
J C
JC
Phelps
M E
ME
D001921:Brain / Q000000981:diagnostic imaging*; D055598:Chemical Phenomena; D002621:Chemistry; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D006801:Humans; D011954:Receptors, Dopamine / Q000032:analysis*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D014055:Tomography, Emission-Computed
D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D011954:Receptors, Dopamine; C051175:3-N-(2-fluoroethyl)spiperone; D013134:Spiperone