Comparative evaluation of two serotonin transporter ligands in the human brain: [¹¹C](+)McN5652 and [¹¹C]cyanoimipramine

Abstract.

Serotonin (5-HT) is considered to be an important transmitter underlying mood and behaviour. Abnormalities of the 5-HT transporter have been suggested in mood disorders, since it is one of the major binding sites of antidepressants. A number of ligands have been developed to visualise the 5-HT transporter in vivo, but only a few have successfully visualised specific binding in vivo. In this study, we comparatively evaluated two ligands for 5-HT transporter, [¹¹C](+)McN5652 and [¹¹C]cyanoimipramine, in the human brain. Brain uptake of [¹¹C](+)McN5652 and [¹¹C]cyanoimipramine was measured with PET in 15 healthy volunteers. Second PET scans were performed after pretreatment with the potent 5-HT reuptake inhibitor clomipramine. Data were analysed as regional brain uptake as well as whole brain uptake. In six healthy volunteers uptake of the two ligands was also measured in the lung since it is one of the high-uptake organs in the body. In the brain, high accumulation was observed in the thalamus and striatum, the regions known to contain high densities of 5-HT transporter, for both [¹¹C](+)McN5652 and [¹¹C]cyanoimipramine. The average ratio of thalamus to cerebellum uptake at 90 min after the tracer injection was approximately 1.6 for [¹¹C](+)McN5652 and 1.7 for [¹¹C]cyanoimipramine, while the ratios obtained after pretreatment with clomipramine were approximately 1.2. However, the whole brain uptake of [¹¹C](+)McN5652 was approximately twice that of [¹¹C]cyanoimipramine, while the lung uptake of [¹¹C](+)McN5652 was approximately half that of [¹¹C]cyanoimipramine. Both [¹¹C](+)McN5652 and [¹¹C]cyanoimipramine showed sufficient specific binding for performance of a quantitative analysis in the brain. [¹¹C](+)McN5652 could be superior because of its higher distribution to the brain.