Wang Huaijun, Sun Xihe, Chen Feng, De Keyzer Frederik, Yu Jie, Landuyt Willy, Vandecaveye Vincent, Peeters Ronald, Bosmans Hilde, Hermans Robert, Marchal Guy, Ni Yicheng
Department of Medical Diagnostic Science, University of Leuven, Leuven, Belgium.
Invest Radiol. 2009 Jan;44(1):44-53. doi: 10.1097/RLI.0b013e31818e5ace.
To document tumoricidal events after intravenous administration of a vascular targeting agent combretastatin A-4-phosphate (CA4P) in rodent liver tumors by using multiparametric magnetic resonance imaging (MRI) in correlation with microangiography and histopathology.
Thirty rhabdomyosarcomas of 8 to 14 mm in diameter were obtained 16 days after implantation in liver lobes of 15 rats. Using a 1.5T magnet and a 4-channel wrist coil, T2-weighted imaging (T2WI), pre- and postcontrast T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and dynamic susceptibility imaging (DSI) with relative blood volume (rBV) and flow (rBF) maps were acquired at baseline, 1 hour, 6 hours, and 48 hours after iv injection of CA4P at 10 mg/kg and vehicle in 9 treated and 6 control rats, respectively. In vivo data including signal intensity (SI), tumor volume, apparent diffusion coefficient (ADC), rBV, and rBF were correlated with ex vivo microangiographic and histopathologic findings.
CA4P-treated tumors (n = 18) grew slower than those (n = 12) of controls (P < 0.05), with vascular shutdown evident on CE-T1WI at 1 hour but more prominent at 6 hours. However, enhanced rim occurred in the periphery 48 hours after treatment, indicating neovascularization. ADC map enabled distinction between necrotic and viable tumors. DSI-derived tumoral rBV and rBF decreased significantly at 1 hour through 6 hours and partly recovered at 48 hours. SI-time curve reflected diverse therapeutic responses between tumor and liver. MRI findings were verified by ex vivo techniques.
Clinical MRI allowed monitoring of CA4P-related vascular shutdown, necrosis, and neovascularization of liver tumors in rats. Single dose of CA4P seemed insufficient for tumor eradication because of evident peripheral residue and recurrence.
通过多参数磁共振成像（MRI）结合微血管造影和组织病理学，记录血管靶向药物磷酸考布他汀A - 4（CA4P）静脉注射后在啮齿动物肝肿瘤中的杀瘤事件。
15只大鼠肝叶植入肿瘤16天后，获取30个直径为8至14毫米的横纹肌肉瘤。使用1.5T磁体和4通道腕部线圈，分别对9只接受治疗的大鼠和6只对照大鼠静脉注射10mg/kg的CA4P及赋形剂，在基线、注射后1小时、6小时和48小时采集T2加权成像（T2WI）、对比剂注射前后的T1加权成像（T1WI）、扩散加权成像（DWI）以及具有相对血容量（rBV）和血流（rBF）图的动态磁敏感成像（DSI）。包括信号强度（SI）、肿瘤体积、表观扩散系数（ADC）、rBV和rBF在内的体内数据与体外微血管造影和组织病理学结果相关联。
CA4P治疗组的肿瘤（n = 18）生长比对照组（n = 12）慢（P < 0.05），在注射后1小时的增强T1WI上可见血管关闭，6小时时更明显。然而，治疗后48小时肿瘤周边出现强化，提示有新生血管形成。ADC图能够区分坏死肿瘤和存活肿瘤。DSI得出的肿瘤rBV和rBF在1小时至6小时显著降低，48小时部分恢复。SI - 时间曲线反映了肿瘤和肝脏之间不同的治疗反应。MRI结果通过体外技术得到验证。
临床MRI能够监测大鼠肝肿瘤中与CA4P相关的血管关闭、坏死和新生血管形成情况。由于明显的周边残留和复发，单剂量的CA4P似乎不足以根除肿瘤。
