New 99M Tc(Co) 3 -Radiolabeled Arylpiperazine Pharmacophore As Potent 5Ht 1A Serotonin Receptor Radiotracer: Docking Studies, Chemical Synthesis, Radiolabeling, and Biological Evaluation Publisher Pubmed



Erfani M¹ ; Malek H² ; Sadat Ebrahimi SE³ ; Hassanzadeh L^{4, 5}
Source: Journal of Labelled Compounds and Radiopharmaceuticals Published:2019

Abstract

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. © 2019 John Wiley & Sons, Ltd.