Carbon-11 labelling of madam in two different positions: A highly selective pet radioligand for the serotonin transporter

Imaging by scintigraphy the serotonin transporter (5-HTT) in the living human brain would be of great value in research on the pathophysiology and treatment of neuropsychiatric disorders such as depression. For that reason, and in order to obtain a selective radiotracer applicable to PET, we report here the carbon-11 labelling of a selective 5-HTT radioligand: N, N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine or MADAM in two different positions: [p-11C-methyl]MADAM and [N-11C-methyl]MADAM. The synthesis of Bu3Sn-ADAM and N-dimethyl-MADAM is described. [p-11C-methyl]MADAM was obtained by a Stille coupling reaction between Bu3Sn-ADAM and [11C]methyl iodide using palladium (0) as a catalyst without (Ia) or with copper chloride as a co-catalyst (Ib). [N-11C-methyl]MADAM was obtained by an N-methylation reaction between N-demethyl-MADAM and [11C]methyl iodide (II). The carbon-11 incorporation yield in [p-11C-methyl]MADAM was 10–30% (Ia and Ib) and in [N-11C-methyl]MADAM was 75-80% (II). The final product in each case was obtained in 30 min total synthesis time, including HPLC purification and with >99% radiochemical purity. Copyright © 2001 John Wiley & Sons, Ltd.