Imaging serotonin transporters using [123I]ADAM SPECT in a parkinsonian primate model

Parkinsonʹs disease (PD) affects multiple neurotransmitter systems. The purpose of this study was to investigate differences in the serotonin transport system between normal and parkinsonian monkeys using 2-([2-([di-methylamino]methyl)phenyl]thio)-5-[123I] iodophenyl-amine([123I]ADAM), a serotonin transporters (SERT) radioligand. The brain single photon emission computed tomography (SPECT) was performed on two normal and one parkinsonian monkey. The parkinsonian monkey was induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle under magnetic resonance imaging (MRI) guidance. Each monkey underwent two [99mTc] TRODAT-1 (a dopamine transporters imaging agent) and two [123I] ADAM brain SPECT scans. After a bolus injection of the radioligand, the SPECT data were acquired over 4 h using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. The striatal uptake of [99mTc]TRODAT-1 was 46% lower in the parkinsonian monkey than those of normal monkeys at 210–240 min post-injection. [123I]ADAM uptake in the midbrain of the parkinsonian monkey was comparable to those of the controls. The uptakes of [123I]ADAM in the striatum, thalamus, and frontal cortex of the parkinsonian monkey, were 31%, 31%, and 23% lower than those of normal monkeys at 210–240 min post-injection, respectively. Our results suggest that [123I]ADAM SPECT has potential for evaluating the serotonin transporter changes in human PD.