title: A novel [99mTc[triple bond]N]2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia.
abstract: A xanthate derivative (L) at the pendant hydroxy group of metronidazole, a nitroimidazole known to possess affinity for hypoxic tumors, has been used as the carrier molecule for targeted delivery of the gamma-emitting radioisotope 99mTc to tumors. The xanthate residues (S2(-)) from two molecules of this ligand (L) were used for chelation with the [99mTcN]2+ intermediate to form a square pyramidal and neutral [99mTcN/L2] complex in >95% yield using a low ligand concentration of 1 mg/mL (approximately 3 x 10(-3) M). Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumor showed selective accumulation of the injected activity in the tumor (1.44 +/- 0.26% per gram 1 h pi) with major clearance through hepatobiliary route. The complex showed high tumor/muscle ratio (2.15 and 3.35 at 1 and 3 h post-injection, respectively) and tumor/blood ratio, which were comparable to hypoxia targeting agents 99mTc-BMS181321 and 99mTc-BRU59-21 reported earlier.
authors.affiliation: Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Madhava B
authors.initials: MB
authors.lastname: Mallia
authors.forename: Anupam
authors.initials: A
authors.lastname: Mathur
authors.forename: Suresh
authors.initials: S
authors.lastname: Subramanian
authors.forename: Sharmila
authors.initials: S
authors.lastname: Banerjee
authors.forename: H D
authors.initials: HD
authors.lastname: Sarma
authors.forename: Meera
authors.initials: M
authors.lastname: Venkatesh
mesh_terms: D000818:Animals; D000860:Hypoxia / Q000175:diagnosis*; D007093:Imidazoles / Q000493:pharmacokinetics; D008024:Ligands; D008795:Metronidazole / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D009593:Nitroimidazoles / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: C403973:BRU 59-21; D007093:Imidazoles; D008024:Ligands; D009593:Nitroimidazoles; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D008795:Metronidazole; C082027:BMS 181321