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Trapping effect on a small molecular drug with vascular-disrupting agent CA4P in rodent H22 hepatic tumor model: in vivo magnetic resonance imaging and postmortem inductively coupled plasma atomic emission spectroscopy.

Abstract
The aim of the present study is to verify the trapping effect of combretastatin A-4-phosphate (CA4P) on small molecular drugs in rodent tumors. Mice with H22 hepatocarcinoma were randomized into groups A and B. Magnetic resonance imaging (MRI) of T1WI, T2WI, and DWI was performed as baseline. Mice in group A were injected with Gd-DTPA and PBS. Mice in group B were injected with Gd-DTPA and CA4P. All mice undergo CE-T1WI at 0 h, 3 h, 6 h, 12 h, and 24 h. Enhancing efficacy of the two groups on CE-T1WI was compared with the signal-to-noise ratio (SNR) calculated. Concentrations of gadolinium measured by ICP-AES in the tumor were compared between groups. On the early CE-T1WI, tumors were equally enhanced in both groups. On the delayed CE-T1WI, the enhancing effect of group A was weaker than that of group B. The SNR and the concentration of gadolinium within the tumor of group A were lower than that of group B at 6 h, 12 h, and 24 h after administration. This study indicates that CA4P could improve the retention of Gd-DTPA in the tumor and MRI allowed dynamically monitoring trapping effects of CA4P on local retention of Gd-DTPA as a small molecular drug.
AuthorsMeng Gao, Nan Yao, Dejian Huang, Cuihua Jiang, Yuanbo Feng, Yue Li, Bin Lou, Fei Peng, Ziping Sun, Yicheng Ni, Jian Zhang
JournalJournal of drug targeting (J Drug Target) Vol. 23 Issue 5 Pg. 436-43 (Jun 2015) ISSN: 1029-2330 [Electronic] England
PMID25582132 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Contrast Media
  • Stilbenes
  • fosbretabulin
  • Gadolinium DTPA
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Carcinoma, Hepatocellular (drug therapy, pathology)
  • Contrast Media (administration & dosage, pharmacokinetics)
  • Disease Models, Animal
  • Gadolinium DTPA (administration & dosage, pharmacokinetics)
  • Liver Neoplasms (drug therapy, pathology)
  • Magnetic Resonance Imaging (methods)
  • Male
  • Mice
  • Spectrophotometry, Atomic (methods)
  • Stilbenes (pharmacology)
  • Time Factors
  • Tissue Distribution

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