[123/125I]RTI‐55, an in vivo label for the serotonin transporter

Abstract

[¹²³I]RTI-55, an iodinated derivative of the cocaine analog 3β-phenyltropane-2β-carboxylic acid methyl ester, was evaluated as an agent for in vivo labeling of the serotonin transporter. Labeling of the precursor of RTI-55 with I-123 was efficient and yielded a high specific activity product. After intravenous injection of [¹²³I]RTI-55 into rats, the tracer accumulated in regions with high densities of serotonin and dopamine uptake sites. The distribution of [¹²³I]RTI-55 binding in areas rich in serotonin uptake sites correlated with [³H]serotonin uptake measured in vitro in the same regions. Specific [¹²³I]RTI-55 binding to serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909. Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66% (in the hypothalamus) to 83% (in the superior colliculi) of specific [¹²⁵I]RTI-55 binding in all areas except in the striatum and the olfactory tubercles (regions rich in dopamine transporters). These results indicate that [^123/125I]RTI-55 binds, although not selectively, to the serotonin transporter in vivo. Furthermore, they suggest that [¹²³I]RTI-55 holds promise as a SPECT imaging agent for the study of the serotonin transporter in humans in health and disease. Published Wiley-Liss, Inc.