Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of human hepatoma cells orthotopically implanted in nude rats.
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.
Hanada
Mitsuharu
M
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, 3-1-98, Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan. mitsuharu-hanada@ds-pharma.co.jp
Baba
Akemi
A
Tsutsumishita
Yasuyuki
Y
Noguchi
Toshihiro
T
Yamaoka
Takashi
T
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D018736:DNA Adducts / Q000032:analysis; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008220:Lymphography; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D051381:Rats; D011923:Rats, Nude; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009944:Organoplatinum Compounds; C406530:miriplatin; D007459:Iodized Oil; D002945:Cisplatin