Synthesis and biological evaluation of 99mTc(CO)3-OH-PP-CS2 for brain receptor imaging

Introduction: 5-HT1A 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 [99mTc (CO) 3(H2O) 3] + core via dithiocarbamate moiety. Methods: 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 [99mTc(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. Results: 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 99mTc(CO)3-OH-PP-CS2. Biodistribution results showed that radio tracer had moderate brain uptake (0.32 ± 0.03 %ID/g at 30 min post injection), Conclusion: This complex may lead to a further development of a radiotracer with specific binding to 5-HT1A receptor.