Radiolabeling, docking studies, in silico ADME and biological evaluation of serotonin with 125I for 5-HTRs imaging

Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors (5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and its receptor dysfunction. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with 125I in a neutral medium, and 125I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify 125I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract uptake of 125I-serotonin was 17.8 ± 0.93% ID/organ after 30 min postinjection and the tracer’s ability to pass the blood–brain barrier. Thus, 125 I-serotonin is a promising single photon emission computed tomography tracer in the detection of 5HTRs.