Cancer Chemotherapy and Pharmacology
Volume 64, Number 3, 473-483, DOI: 10.1007/s00280-008-0895-3Open Access

Original Article

Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of tumors implanted in rat livers by inducing platinum-DNA adducts to form and massive apoptosis

Mitsuharu Hanada, Akemi Baba, Yasuyuki Tsutsumishita, Toshihiro Noguchi, Takashi Yamaoka, Nobuyoshi Chiba and Fumio Nishikaku

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Abstract

Background  

Miriplatin (formerly SM-11355), a novel lipophilic platinum complex developed to treat hepatocellular carcinoma, is administered into the hepatic artery using an oily lymphographic agent (Lipiodol Ultra-Fluide®) as a carrier. We clarified the usefulness of miriplatin as an agent for transarterial chemoembolization.

Methods  

Platinum compounds released from miriplatin into serum, medium and Earle’s balanced salt solution were examined. Then, miriplatin and cisplatin were administered to rats bearing hepatoma AH109A tumors in livers. Platinum concentrations in tissues and DNA were assessed.

Results  

Miriplatin showed a more sustained release than cisplatin. Dichloro[(1R, 2R)-1, 2-cyclohexane diamine-N, N′]platinum, the most abundant platinum compound released from miriplatin, was as effective as cisplatin in inhibiting the growth of cells. Miriplatin was selectively disposed of in tumors, maintained in tumors longer than cisplatin and caused apparent tumor regression inducing platinum-DNA adducts to form and massive apoptosis.

Conclusion  

Miriplatin appears to be a suitable chemotherapeutic agent for transarterial chemoembolization.

Keywords  Miriplatin - Lipiodol - Platinum-DNA adducts - Apoptosis - Hepatocellular carcinoma

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