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.
Pharm Res. 2012 Jan;29(1):178-86. doi: 10.1007/s11095-011-0525-3. Epub 2011 Jul 26.
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.
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.
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.
Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.
评估血管破坏剂（combretastatin 衍生物，Cderiv）对载药聚合物胶束系统靶向肿瘤的效果，这些载药聚合物胶束系统含有诊断性磁共振成像（MRI）对比剂或治疗性抗癌药物。
在注射载药聚合物胶束 MRI 对比剂前 72 h 预先给予 Cderiv。通过电感耦合等离子体发射光谱法（ICP）和 MRI 评估 Cderiv 预处理前后对结肠 26 鼠肿瘤中 MRI 对比剂累积的影响。
当在注射 MRI 对比剂前 72 h 给予 Cderiv 时，MRI 对比剂在肿瘤组织中的积累明显增加。在注射对比剂后 24 h，肿瘤区域的 T1 加权图像显示出显著的信号增强。在 T1 加权图像中，部分肿瘤而非整个肿瘤出现显著的 T1 信号增强。这些结果表明，Cderiv 预处理显著增强了肿瘤血管的通透性。载阿霉素聚合物胶束的抗肿瘤活性在 44As3 人胃癌硬癌荷瘤裸鼠中，通过 Cderiv 预处理后抑制了肿瘤生长。
Cderiv 预处理增强了肿瘤的通透性，导致载药聚合物胶束系统在实体瘤中的积累增加。
