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

[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.