title: Design and evaluation of "3 + 1" mixed ligand oxorhenium and oxotechnetium complexes bearing a nitroaromatic group with potential application in nuclear medicine oncology.
abstract: The synthesis and evaluation of a series of oxotechnetium and oxorhenium complexes containing a nitroaromatic moiety as potential radiopharmaceuticals for targeting tumour hypoxia is presented. 99mTc labelling was performed in high yield (>85%) and radiochemical purity (>90%). Their structure was corroborated by means of the rhenium complexes. Reduction potentials were in the range for bioreducible compounds. 99mTc complexes III-VI were selected for "in vivo" experiments in view of the results of cytotoxicity studies. Biodistribution in normal animals was characterized by high initial blood, lung and liver uptake, fast blood and soft tissue depuration and preferential excretion via the hepatobiliary system. Initial tumour uptake was moderate but tumour/muscle ratios for complexes III and IV, were favourable at all time points. Although the results are encouraging further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.
authors.affiliation: Cátedra de Radioquímica, Facultad de Química, General Flores 2124, 11800 Montevideo, Uruguay.
authors.forename: J
authors.initials: J
authors.lastname: Giglio
authors.forename: A
authors.initials: A
authors.lastname: Rey
authors.forename: H
authors.initials: H
authors.lastname: Cerecetto
authors.forename: I
authors.initials: I
authors.lastname: Pirmettis
authors.forename: M
authors.initials: M
authors.lastname: Papadopoulos
authors.forename: E
authors.initials: E
authors.lastname: León
authors.forename: A
authors.initials: A
authors.lastname: Monge
authors.forename: A
authors.initials: A
authors.lastname: López de Ceráin
authors.forename: A
authors.initials: A
authors.lastname: Azqueta
authors.forename: M
authors.initials: M
authors.lastname: González
authors.forename: M
authors.initials: M
authors.lastname: Fernández
authors.forename: A
authors.initials: A
authors.lastname: Paolino
authors.forename: A
authors.initials: A
authors.lastname: León
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015902:Gamma Cameras; D000860:Hypoxia; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental; D009578:Nitrobenzenes / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012211:Rhenium / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D008024:Ligands; D009578:Nitrobenzenes; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; C015428:perrhenate; D012211:Rhenium