Antitumour and Toxicity Evaluation of a Ru(II)-Cyclopentadienyl Complex in a Prostate Cancer Model by Imaging Tools

Author(s):

Lurdes Gano, Teresa Pinheiro, António P. Matos, Francisco Tortosa, Tiago F. Jorge, Maria S. Gonçalves, Marta Martins, Tânia S. Morais, Andreia Valente, Ana I. Tomaz, Maria H. Garcia and Fernanda Marques*   Pages 1262 - 1275 ( 14 )

Abstract:

<P>Background: Ruthenium complexes have been extensively investigated for their prospective value as alternatives to cisplatin. Recently, we reported the in vitro anticancer properties of a family of organometallic ruthenium( II)-cyclopentadienyl complexes and have explored their mechanism of action. </P><P> Objective: The purpose of this study was to evaluate the in vivo antitumour efficacy and toxicity of one of these Ru(II) compounds, [RuCp(mTPPMSNa)(2,2′-bipy)][CF3SO2] (TM85) which displayed an interesting spectrum of activity against several cancer cells. </P><P> Methods: Studies to assess the antitumour activity and toxicity were performed in a metastatic prostate (PC3) mice model using ICP-MS, nuclear microscopy, elemental analysis and Transmission Electron Microscopy (TEM). </P><P> Results: TM85 showed low systemic toxicity but no significant tumour reduction, when administered at tolerated dose (20mg/kg) over 10 days. Ru was mainly retained in the liver and less in kidneys, with low accumulation in tumour. Increased bilirubin levels, anomalous Ca and Fe concentrations in liver and mitochondria alterations were indicative of liver injury. The hepatotoxicity observed was less severe than that of cisplatin and no nephrotoxicity was found. </P><P> Conclusion: Under the experimental conditions of this study, TM85 is less toxic than cisplatin, induces similar tumour reduction and avoids the formation of metastatic foci. No renal toxicity was observed by the analysis of creatinine levels and the effective renal plasma flow by 99mTc-MAG3 clearance. Hence, it can be considered a valuable compound for further studies in the field of Ru-based anticancer drugs.</P>

Keywords:

Ru(II) complexes, in vivo studies, antitumour activity, toxicity, transmission electron microscopy (TEM), microprobe imaging.

Affiliation:

Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela LRS, Lisboa, Departamento de Engenharia e Ciencias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela LRS, Lisboa, Centro de Investigacao Interdisciplinar Egas Moniz, Campus Universitario, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Instituto de Anatomia Patologica, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Centro de Quimica e Bioquimica, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Faculdade de Medicina Veterinaria, Universidade de Lisboa, Av. da Universidade Tecnica, Polo Universitario da Ajuda 1300-477 Lisboa, Instituto de Medicina Molecular-Joao Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Centro de Quimica Estrutural, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Centro de Quimica Estrutural, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Centro de Química Estrutural, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Centro de Quimica Estrutural, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Centro de Ciencias e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, km 139.7, 2695-066 Bobadela LRS, Lisboa

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