New 99m Tc(CO)3 -radiolabeled arylpiperazine pharmacophore as potent 5HT1A 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-carbon linker and radiolabeled 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 radiolabeled 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 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 5HT1A receptors.
['Erfani|Mostafa|M|0000-0002-5674-1575', 'Malek|Hadi|H|', 'Sadat Ebrahimi|Seyed Esmaeil|SE|', 'Hassanzadeh|Leila|L|0000-0001-8958-8848']
D000818:Animals D001921:Brain D057930:Click Chemistry D006801:Humans D007553:Isotope Labeling D008297:Male D062105:Molecular Docking Simulation D015609:Organotechnetium Compounds D000077489:Piperazine D011487:Protein Conformation D011854:Radiochemistry D051381:Rats D044405:Receptor, Serotonin, 5-HT2C D014018:Tissue Distribution
docking 1-(2-methoxyphenyl)piperazine (MPP) WAY100635 2-ethynylpyridine click chemistry 5HT1A homology model