title: Synthesis of 99mTc-nitrido heterocomplex of piperidine and in vitro and in vivo evaluation of its affinity for sigma receptors.
abstract: Sigma receptors are overexpressed in various types of cancer cells, making ligands that bind to these receptors attractive vectors for targeting radiation to specific sites for the imaging and therapy of oncologic disorders. In this paper, we report the synthesis of a dithiocarbamate derivative of 4-amino-N-benzylpiperidine and its radiolabeling with the [(99m)TcN(PNP)](2+) metal synthon. The radiolabeled tracer has been evaluated for sigma-receptor specificity. The radiochemical purity of the (99m)Tc-complex was >98%. The in vitro cell-binding and competition studies of the complex showed affinity and specificity toward fibrosarcoma and melanoma cells. In vivo studies carried out in mice bearing melanoma and fibrosarcoma tumors showed tumor uptakes of 1% and 1.9%, respectively, at 3 hours postinjection. In vivo blocking studies were carried out, using (+)-pentazocine, a sigma-receptor-specific agent where approximately 40% decrease in the tumor uptake was observed. The affinity of [(99m)TcN(PNP)Pip-DTC](+) complex for sigma-receptor sites ascertained through in vitro and in vivo studies makes it a potential agent for further investigation.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Drishty
authors.initials: D
authors.lastname: Satpati
authors.forename: Ketaki
authors.initials: K
authors.lastname: Bapat
authors.forename: Haladhar Deb
authors.initials: HD
authors.lastname: Sarma
authors.forename: Kanchan
authors.initials: K
authors.lastname: Kothari
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D005354:Fibrosarcoma / Q000000981:diagnostic imaging*; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D009292:Narcotic Antagonists / Q000494:pharmacology; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D010423:Pentazocine / Q000494:pharmacology; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: C528644:(99m)TcN(PNP)Pip-DTC; D009292:Narcotic Antagonists; D015609:Organotechnetium Compounds; D017480:Receptors, sigma; D010423:Pentazocine