New 99m Tc-(CO) 3 -radiolabeld arylpiperazine pharmacophore as potent 5-HT 1A serotonin receptor radiotracer: Docking studies, chemical synthesis, radiolabeling and biological evaluation.

In spite of previous efforts there is lack of a radiotracer for imaging the 5HT1A receptor density in human brain which is involved in several neurological brain disorders. The aim of this study was to prepare a new derivative of 1-(2-methoxyphenyl) piperazine (MPP) as a main chemical structure of 5HT1A receptor antagonist with 3-carbons linker and radio-labeled by [99m Tc][Tc (CO)3 (H2 O)3 ]+ precursor. Docking studies before chemical synthesis, showed similar fashion of interaction for both WAY100635 (potent 5HT1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc-(CO)3 group in the structure of new ligand. MPP-(CH2 )3 -N3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radio-labeled by addition of 2-ethynylpyridine and [99m Tc][Tc (CO)3 (H2 O)3 ]+ precursor in one pot procedure (more than 95% radiochemical efficiency) through click chemistry method. After incubation, radiotracer was found stable in vitro up to 2 hours. Binding assays showed about 33% specific binding of radiotracer to the 5HT1A receptors. Brain bio-distribution studies indicated (0.26 ± 0.05)% ID/g hippocampus uptake at 30 min post injection which its specificity was verified through blocking studies. These results suggested that new designed radio-ligand might serve as a potent SPECT imaging agent to estimate status of 5HT1A receptors.