title: Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems.
abstract: OBJECTIVE
  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 carcinoma-bearing nude mice.
  
  
  CONCLUSIONS
  Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.
authors.affiliation: Medical Engineering Laboratory, Research Center for Medical Science, The Jikei University School of Medicine, Nishi-shinbashi 3-25-8, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Harada
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawano
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Maitani
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hori
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Misato
authors.initials: M
authors.lastname: Takigahira
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001632:Bibenzyls / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002199:Capillary Permeability; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009369:Neoplasms / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000903:Antibiotics, Antineoplastic; D001632:Bibenzyls; C571791:Cderiv; D004337:Drug Carriers; D008823:Micelles; C040105:combretastatin; D004317:Doxorubicin