SYNTHESIS AND IN-VIVO STUDIES OF A SELECTIVE LIGAND FOR THE DOPAMINE TRANSPORTER - BETA-(4-[I-125]IODOPHENYL)TROPAN-2-BETA-CARBOXYLIC ACID ISOPROPYL ESTER ([I-125]RTI-121)

A selective ligand for the dopamine transporter 3 beta-(4-iodophenyl)t ropan-2 beta-carboxylic acid isopropyl ester (RTI-121) has been labele d with iodine-125 by electrophilic radioiododestannylation. The [I-125 ]RTI-121 was obtained in good yield (86 +/- 7%, n = 3) with high radio chemical purity(>99%) and specific radioactivity (1210-1950 mCi/mu mol ). After i.v. administration of [I-125]Rn-121 to mice, the rank order of regional brain tissue radioactivity (striatum > olfactory tubercles much greater than cortex, hippocampus, thalamus, hypothalamus, cerebe llum) was consistent with dopamine transporter labeling, Specific in p ike binding in striatum and olfactory tubercles was saturable, and was blocked by the dopamine transporter ligands GBR 12,909 and (+/-)-nomi fensine. By contrast, binding was not reduced by paroxetine, a seroton in transporter inhibitor, or desipramine, a norepinephrine transporter inhibitor. A variety of additional drugs having high affinities for r ecognition sites other than the neuronal dopamine transporter also had no effect, The [I-125]RTI-121 binding in striatum and olfactory tuber cles was inhibited by d-amphetamine in dose-dependent fashion. Nonmeta bolized radioligand represents 85% of the signal observed in extracts of whole mouse brain. Thus, [I-125]RTI-121 is readily prepared, and is a useful tracer for dopamine transporter studies in vivo.