New 99m Tc(CO) 3 ‐radiolabeled arylpiperazine pharmacophore as potent 5HT 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 5HT 1A 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 5HT 1A receptor antagonist with 3‐carbon linker and radiolabeled by [ 99m Tc][Tc(CO) 3 (H 2 O) 3 ] + precursor. Docking studies before chemical synthesis showed similar fashion of interaction for both WAY100635 (potent 5HT 1A receptor antagonist) and new designed ligand, despite of addition of 99m Tc(CO) 3 group in the structure of new ligand. MPP‐(CH 2 ) 3 ‐N 3 was synthesized via three efficient and reliable chemical synthesis steps (more than 80% yield) then radiolabeled by addition of 2‐ethynylpyridine and [ 99m Tc][Tc(CO) 3 (H 2 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 5HT 1A receptors. Brain biodistribution studies indicated (0.26 ± 0.05)% ID/g hippocampus uptake at 30 minutes post injection, which its specificity was verified through blocking studies. These results suggested that new designed radioligand might serve as a potent SPECT imaging agent to estimate status of 5HT 1A receptors.