Evaluation of Deoxyribonucleic Acid Toxicity Induced by the Radiopharmaceutical 99mTechnetium-Methylenediphosphonic Acid and by Stannous Chloride in Wistar Rats

Molecules

José Carlos Pelielo De Mattos²  Vanessa Coutinho de Matos²  Michelle Pinheiro Rodrigues²  Marcia Betânia Nunes de Oliveira²  Flavio José S. Dantas²  Sebastião David Santos-Filho²  Mario Bernardo-Filho¹ 

[1] Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, Rio de Janeiro 20551-030, Brazil;

关键词: stannous chloride;    ^99mTc-MDP;    genotoxicity;    mutagenicity;    Comet assay;    micronucleus test;   

DOI  :  10.3390/molecules171112974

来源: mdpi

【 摘 要 】

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 (SnCl₂) being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the ^99mTc-MDP(methylene diphosphonate used for bone SPECT) and SnCl₂ 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), SnCl₂ 500 μg/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 SnCl₂ 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 SnCl₂ 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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.