PHARMACOLOGICAL CONTROL OF LUNG METASTASES OF SOLID TUMORS BY A NOVELRUTHENIUM COMPLEX

Imidazolium ns-imidazoledimethylsulphoxidetetrachlororuthenate ImH[tra ns-RuCl4(DMSO)Im] (NAMI-A), a ruthenium compound that replaces Na+ wit h ImH(+) in the molecule of Na[trans-RuCl4(DMSO)Im] (NAMI), was studie d for the anti-metastasis effects in models of solid metastasizing tum ours of the mouse. NAMI-A, given i.p. at 35 mg/kg/day for six consecut ive days, a dose equimolar to that of NAMI, to mice bearing Lewis lung carcinoma and MCa mammary carcinoma, markedly reduces lung metastasis weight by 80-90%, with an effect equal or even superior to that of NA MI, depending on the experimental system adopted. Correspondingly, NAM I-A increases the content of connective tissue in the tumour matrix, a round blood vessels, and in the tumour capsule, augments the percentag e of tumour cells in G(2)/M phase and reduces the amount of CD45(+) ce lls infiltrating the tumour parenchyma. The effects of the same doses on spleen lymphocytes correspond to an increase of CD8(+) subset witho ut any change of the distribution of cells in G(0)/G(1), S and G(2)/M phases. The study shams that NAMI-A behaves similarly to NAMI, on the several parameters examined in comparison experiments and therefore we suggest to credit NAMI-A with all the biological actions already desc ribed for NAR?II during the last 3 years. The replacement of Na+ with ImH(+) therefore, besides the better chemical stability of the molecul e, confers to [trans-RuCl4(DMSO)Im](-) a closer similarity with a true drug to be used in humans, and suggests this molecule for future stud ies of preclinical toxicology and phase I and II clinical trials. (C) 1998 Lippineott-Raven Publishers.