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New 99m Tc(CO) 3 ‐radiolabeled arylpiperazine pharmacophore as potent 5HT 1A serotonin receptor radiotracer: Docking studies, chemical synthesis, radiolabeling, and biological evaluation
Author(s) -
Erfani Mostafa,
Malek Hadi,
Sadat Ebrahimi Seyed Esmaeil,
Hassanzadeh Leila
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3709
Subject(s) - chemistry , radioligand , radiosynthesis , pharmacophore , biodistribution , piperazine , 5 ht receptor , receptor , chemical synthesis , ligand (biochemistry) , lead compound , stereochemistry , docking (animal) , serotonin , in vitro , in vivo , biochemistry , organic chemistry , medicine , microbiology and biotechnology , nursing , biology
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.