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

Cancer Chemother Pharmacol. 2009 Aug;64(3):473-83. doi: 10.1007/s00280-008-0895-3. Epub 2008 Dec 24.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Chemoembolization, Therapeutic / methods*
  • Cisplatin / pharmacology
  • DNA Adducts / metabolism
  • Delayed-Action Preparations
  • Drug Carriers / administration & dosage
  • Drug Screening Assays, Antitumor
  • Hepatic Artery
  • Infusions, Intra-Arterial
  • Iodized Oil / administration & dosage*
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / pathology
  • Lymphography
  • Male
  • Neoplasm Transplantation
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / pharmacology*
  • Rats

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Delayed-Action Preparations
  • Drug Carriers
  • Organoplatinum Compounds
  • miriplatin
  • Iodized Oil
  • Cisplatin