Carbon‐11 labelling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter

Abstract

Abstract 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 ‐ 11 C‐methyl]MADAM and [ N ‐ 11 C‐methyl]MADAM. The synthesis of Bu 3 Sn‐ADAM and N ‐dimethyl‐MADAM is described. [ p ‐ 11 C‐methyl]MADAM was obtained by a Stille coupling reaction between Bu 3 Sn‐ADAM and [ 11 C]methyl iodide using palladium (0) as a catalyst without (Ia) or with copper chloride as a co‐catalyst (Ib). [ N ‐ 11 C‐methyl]MADAM was obtained by an N ‐methylation reaction between N ‐demethyl‐MADAM and [ 11 C]methyl iodide (II). The carbon‐11 incorporation yield in [ p ‐ 11 C‐methyl]MADAM was 10–30% (Ia and Ib) and in [ N ‐ 11 C‐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.