[125 I]3β-(4-ethyl-3-iodophenyl)nortropane-2β-carboxylic acid methyl ester ([125I]EINT):: A potent and selective radioligand for the brain serotonin transporter

The binding characteristics of [I-125] 3 beta-(4-ethyl-3-iodophenyl)nortropane-2 beta -carboxylic acid methyl ester ([I-125]EINT), a high-affinity selective ligand for the serotonin transporter (5-HTT), and its binding characteristics to rat brain membranes were determined. [I-125]EINT binding to rat cerebral cortex membranes was saturable and reversible, and its specific binding represented approximately 90% of the total binding. [I-125]EINT labeled a single site with K-d = 0.22 +/- 0.03 nM and B-max = 583 +/- 38 fmol/mg protein. Kinetic analysis revealed a t(1/2) for association and dissociation of 20 and 24 min, respectively. Pharmacological characterization of [I-125]EINT confirmed its high specificity for the 5-HTT. The pattern of brain region distribution in vivo of intravenously administered [I-125]EINT indicated greater accumulation of the radioligand in 5-HTT-rich brain regions. However, the signal-to-background ratio was low. Thus, [I-125]EINT appears to be a useful radioligand for studying the 5-HTT in vitro, but it may not be a good in vivo ligand. Synapse 41:241-247, 2001. (C) 2001 Wiley-Liss, Inc.