title: Synthesis, Characterization, and Preclinical Evaluation of (99m)Tc-Labeled Macrobicyclic and Tricyclic Chelators as Single Photon Emission Computed Tomography Tracer.
abstract: The novel tetraaza macrobicyclic chelator 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-2,10-dione (TBPD) and pentaaza macrotricyclic chelator 9-oxa-3,6,12,15,21-pentaazatricyclo[15,3,2,1]trieicos-1(21),17,19-triene-2,7,11,16-tetradione (OPTT) were synthesized, characterized, and radiolabeled with (99m)Tc to produce (99m)Tc-TBPD and (99m)Tc-OPTT. These radiolabeled complexes were prepared with high radiolabeling yield, radiochemical purity, and good in vitro stability up to 24 h. The labeling efficiency of (99m)Tc-TBPD and (99m)Tc-OPTT was found 98% and 97%. In vitro serum stability of (99m)Tc-TBPD was found to be 95.2%, while that of (99m)Tc-OPTT 94.2% up to 24 h. Blood kinetics experiments of (99m)Tc-labeled complexes showed biphasic pattern of blood clearance. About 99.57 ± 0.89% activity of (99m)Tc-TBPD and 99.42 ± 0.88% activity of (9m)Tc-OPTT were cleared off blood stream at 24 h postadministration. The biological half-life of (99m) Tc-TBPD was observed: t1/2(F) 1 h 5 min and t1/2(S) 12 h and biological half-life of (99m)Tc-OPTT was observed: t1/2(F) 1 h 10 min and t1/2(S) 9 h 50 min, respectively. The biodistribution studies revealed that maximum uptake of (99m)Tc-TBPD was found in liver, concluded that excretory pathway is hepatobiliary, while that of (99m)Tc-OPTT was renal as well as hepatobiliary. The negligible activity observed in stomach confirming the stability of radiolabeled complex in biological milieu. In vitro cytotoxicity study of TBPD and OPTT did not show any considerable antiproliferative activity against cancer cells of human cervical SW756, HeLa, and glioblastoma U-87, U373 cell lines.
authors.affiliation: Department of Chemistry, Centre of Advanced Study, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Neelam
authors.initials: N
authors.lastname: Yadav
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Road, Timarpur, Delhi, 110054, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Brig. S. K. Mazumdar Road, Timarpur, Delhi, 110054, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.affiliation: Department of Chemistry, Centre of Advanced Study, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Bachcha
authors.initials: B
authors.lastname: Singh
mesh_terms: D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D002614:Chelating Agents
keywords: 99mTechnetium; DFT; cancer; ligand; macrocyclic chelators; radiolabeling