Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents

• Published in: Nuclear medicine and biology 2013-02, Vol.40 (2), p.227-232
• Main Authors: Hassanzadeh, Leila, Erfani, Mostafa, Najafi, Reza, Shafiei, Mohammad, Amini, Mohsen, Shafiee, Abbass, Ebrahimi, Seyed Esmaeil Sadat
• Format: Article
• Language: English
• Subjects: 5-HT1A receptor; 99mTc-tricarbonyl; Animals; Azides - chemistry; Chemistry Techniques, Synthetic; Click Chemistry; Isotope Labeling; Molecular Imaging - methods; Organotechnetium Compounds - chemistry; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacokinetics; Radiology; Rats; Receptor, Serotonin, 5-HT1A - metabolism; Triazoles - chemistry; WAY100635
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2012.10.004

Abstract Introduction It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT1A antagonist WAY100635, is found in numerous selective 5-HT1A imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with99m Tc (CO)3 via click chemistry. Methods The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [99m Tc] [(H2 O) 3CO 3 ]+ and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. Results Triazole complex was labeled by99m Tc-tricarbonyl and its radiochemical yield was more than > 95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24 h period. The calculated partition coefficient (logP) was 0.34 ± 0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT1A receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40 ± 0.08 %ID/g at 30 min post injection. Conclusions Results indicate that this99m Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT1A receptors and presented suitable characters for its use as a CNS imaging agent.