Synthesis and biological evaluation of [99m]Tc[CO][3]-OH-PP-CS[2] for brain receptor imaging

ABSTRACT

5-HT[1A] receptor is related with a variety of neuropsychiatric disorders. In this study a phenolic analogue derived from DWAY [Desmethyl WAY-100635 [N-[2-[1-[4-[2-methoxyphenyl]piperazinyl]-ethyl]]-N-[2-pyridinyl] cyclohexanecarboxamide]] is used to design the desired structure of 5-HT1A receptor imaging agents after labeling with [[99m]Tc [CO] [3][H[2]O] [3]] [+] core via dithiocarbamate moiety. 2-[piperazin-1-yl] phenol Dithiocarbamate was synthesized by the reaction of 2-[piperazin-1-yl] phenol with an equivalent amount of carbon disulfide in KOH solution then radiolabeled with [[99m]Tc[CO][3][H2O][3][+] core. Radioligand chemical analysis involved high-performance liquid chromatography methods. Radioconjugate stability and lipophilicity were determined. Biodistribution of labeled compound was studied in rats. The final complex was characterized by HPLC and its radiochemical purity was more than 90%. In vitro stability studies have shown the complex was stable at least 6-hrs after labeling at room temperature. The n-octanol/water partition coefficient experiment demonstrated Log P = 0.74 for [99m]Tc[CO][3]-OH-PP-CS[2]. Biodistribution results showed that radio tracer had moderate brain uptake [0.32 +/- 0.03%ID/g at 30 min post injection]. This complex may lead to a further development of a radiotracer with specific binding to 5-HT[1A] receptor