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.

• Combretastatin A-4-phosphate (CA4P)
• inductively coupled plasma atomic emission spectroscopy (ICP-AES)
• magnetic resonance imaging (MRI)
• trapping effect
• tumor

Acknowledgements

We thank Miss Yun Ji and Miss Qingqing Wang, Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, for their wonderful work in molding and MRI scanning.

Declaration of interest

This work was partially supported by the National Natural Science Foundation of China (Nos. 81071828 and 81001379), the 333 Project in Jiangsu Province (BRA2012211), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. ZJ11175), Jiangsu Provicial Qing Lan Project, and CZC Pharmaceutical and Technology Co., Ltd partly supported by Nanjing & Qixia District 321 Project of Special Talent Finance, China.