title: Evaluation of deoxyribonucleic acid toxicity induced by the radiopharmaceutical 99mTechnetium-Methylenediphosphonic acid and by stannous chloride in Wistar rats.
abstract: Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc) is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT) due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl(2)) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl(2) were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control), cyclophosphamide 50 mg/kg b.w. (positive control), SnCl(2) 500 &#956;g/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay) and 36 h after, for micronucleus test. The data showed that both SnCl(2) and 99mTc-MDP-induced deoxyribonucleic acid (DNA) strand breaks in rat  total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to  induce a significant DNA strand breaks increase in in vivo assays. Taken together, the  data presented here points to the formation of a complex between SnCl(2) in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of  nuclear medicine.
authors.affiliation: Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. jcmattos@uerj.br
authors.forename: José Carlos Pelielo De
authors.initials: JC
authors.lastname: Mattos
authors.forename: Vanessa Coutinho de
authors.initials: VC
authors.lastname: Matos
authors.forename: Michelle Pinheiro
authors.initials: MP
authors.lastname: Rodrigues
authors.forename: Marcia Betânia Nunes de
authors.initials: MB
authors.lastname: Oliveira
authors.forename: Flavio José S
authors.initials: FJ
authors.lastname: Dantas
authors.forename: Sebastião David
authors.initials: SD
authors.lastname: Santos-Filho
authors.forename: Mario
authors.initials: M
authors.lastname: Bernardo-Filho
authors.forename: Adriano
authors.initials: A
authors.lastname: Caldeira-de-Araujo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D004249:DNA Damage; D004912:Erythrocytes / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D019275:Radiopharmaceuticals / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013669:Technetium Tc 99m Medronate / Q000633:toxicity*; D017971:Tin Compounds / Q000633:toxicity*
chemical_list: D019275:Radiopharmaceuticals; D017971:Tin Compounds; C023599:stannous chloride; D013669:Technetium Tc 99m Medronate