The SPECT tracer [123I]ADAM binds selectively to serotonin transporters: a double-blind, placebo-controlled study in healthy young men

The tracer I-123-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ([I-123]ADAM) has been developed to image serotonin transporters (SERTs) with SPECT. Preclinical studies have shown that [I-123]ADAM binds selectively to SERTs. Moreover, initial human studies have shown that [I-123]ADAM binding could be blocked by selective serotonin reuptake inhibitors (SSRIs). However, in humans it has not been proven that [I-123]ADAM binds selectively to SERTs. We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [I-123]ADAM. To evaluate the selectivity of binding, four participants were pretreated (double-blinded design) with placebo, four with paroxetine (20 mg) and four with the dopamine/norepinephrine blocker methylphenidate (20 mg). SPECT studies were performed on a brain-dedicated system (Neurofocus), and the SPECT images were coregistered with individual MR scans of the brain. ADAM binding in SERT-rich brain areas and cerebellar cortex (representing non-specific binding) was assessed by drawing regions of interest (ROIs) on the individual MR images. Specific to non-specific ratios were used as the outcome measure. We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylphenidate-pretreated participants. No such difference was found between groups pretreated with placebo or methylphenidate. Our preliminary findings suggest that [I-123]ADAM binds selectively to SERTs in human brain.