Miriplatin is a lipophilic
platinum complex which contains
myristates as leaving groups and diaminocyclohexane as a carrier
ligand. In order to examine in vivo the antitumor activities of
miriplatin suspended in an oily lymphographic agent (
Lipiodol Ultra-Fluide, LPD) against human
hepatocellular carcinoma (HCC) after the intra-hepatic arterial administration, we have developed a novel orthotopic model of HCC in which the human
hepatoma cell line Li-7 was successively implanted and maintained in the liver of nude rats. Li-7
tumors established in nude rat livers displayed a trabecular structure similar to their original morphology, and were exclusively supplied by the hepatic artery, suggesting that they exhibited in part the conditions of human HCC.
Miriplatin suspended in LPD (
miriplatin/LPD) administered into the hepatic artery of this model dose-dependently inhibited the growth of Li-7
tumors without markedly enhancing
body weight loss and caused a significant reduction in the growth rate at a dose of 400 microg/head compared to LPD alone. In addition, at the therapeutic dose,
miriplatin/LPD as well as
cisplatin suspended in LPD (400 microg/head) was shown to be more active than
zinostatin stimalamer suspended in LPD (20 microg/head) against Li-7
tumors after a single intra-hepatic arterial administration. These results suggest
miriplatin to be a suitable candidate for use in transarterial chemoembolization.