A new iodinated tropane derivative (β‐CDIT) for in vivo dopamine transporter exploration: Comparison with β‐CIT

SPECT exploration of the dopamine transporter with tropane derivatives such as β‐CIT has already produced very valuable information in humans. However, the high affinity of this tracer for both dopamine and serotonin transporters and its slow in vivo kinetics provide the best images in humans more than 20 h after injection. In order to improve those properties, we performed structural changes in the tropane structure in the phenyl and nitrogen substituents for higher affinity and specificity and obtained a promising ligand, 2β‐carbomethoxy‐3β‐(3′, 4′ diclorophenyl)‐8‐(3‐iodoprop‐2E‐enyl) nortropane (β‐CDIT). This iodinated ligand was characterized in vitro and in vivo in the rat in comparison with β‐CIT. In vitro competition studies revealed that β‐CIT and β‐CDIT similarly inhibited the binding of [ 3 H]GBR 12935 (Ki = 27.5 and 29.0 nM, respectively). In contrast, competition studies with [ 3 H]paroxetine and [ 3 H]nisoxetine showed that β‐CDIT had a lower affinity for the serotonin transporter than β‐CIT (Ki = 50 and 3 nM, respectively) and also a lower affinity for the noradrenaline transporter than β‐CIT (Ki = 500 and 80 nM, respectively). In vivo studies in the rat showed that there was high and rapid uptake of [ 125 I] β‐CDIT in the striatum. In addition, preinjection of GBR 12909 prevented accumulation of this ligand in the striatum by 80%, whereas only a 30% decrease was obtained for [ 125 I]β‐CIT. It seems, therefore, that the combination of aromatic and nitrogen substitution improves the properties of tropane derivatives to provide an exclusive dopamine transporter ligand potentially usable in SPECT. Synapse 26:72–80, 1997. © 1997 Wiley‐Liss, Inc.