Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems

Kouichi Shiraishi, Yoshiko Harada, Kumi Kawano, Yoshie Maitani, Katsuyoshi Hori, Kazuyoshi Yanagihara, Misato Takigahira, Masayuki Yokoyama

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: To evaluate effect of a vascular disrupting agent, a combretastatin derivative (Cderiv), on tumor targeting for polymeric micelle carrier systems, containing either a diagnostic MRI contrast agent or a therapeutic anticancer drug. Methods: Cderiv was pre-administered 72 h before polymeric micelle MRI contrast agent injection. Accumulation of the MRI contrast agent in colon 26 murine tumor was evaluated with or without pretreatment of Cderiv by ICP and MRI. Results: Significantly higher accumulation of the MRI contrast agent was found in tumor tissues when Cderiv was administered at 72 h before MRI contrast agent injection. T 1-weighted images of the tumor exhibited substantial signal enhancement in tumor area at 24 h after the contrast agent injection. In T 1-weighted images, remarkable T 1-signal enhancements were observed in part of tumor, not in whole tumor. These results indicate that Cderiv pretreatment considerably enhanced the permeability of the tumor blood vessels. Antitumor activity of adriamycin encapsulated polymeric micelles with the Cderiv pretreatment suppressed tumor growth in 44As3 human gastric scirrhous carcinomabearing nude mice. Conclusions: Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalPharmaceutical research
Volume29
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

Keywords

  • Cderiv
  • MRI study
  • Polymeric micelle MRI contrast agent
  • Tumor permeability
  • Tumor vascular disrupting agent

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Fingerprint Dive into the research topics of 'Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems'. Together they form a unique fingerprint.

  • Cite this