Department of Radiology, University Hospitals, University of Leuven, Leuven, Belgium.
Eur Radiol. 2010 Aug;20(8):2013-26. doi: 10.1007/s00330-010-1743-5. Epub 2010 Feb 25.
To evaluate effects of a vascular-disrupting agent on rodent tumour models.
Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [(18)F]fluorodeoxyglucose micro-positron emission tomography ((18)F-FDG microPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUV(max)) from FDG microPET were quantified and correlated with postmortem microangiography and histopathology.
In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUV(max) dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05).
The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment.
评估血管破坏剂对啮齿动物肿瘤模型的作用。
20 只患有肝横纹肌肉瘤的大鼠静脉注射 20mg/kg 的 ZD6126，并用 10 只接受载剂治疗的大鼠作为对照。在治疗后 1h、24h 和 48h 分别使用 1.5T MRI 进行扩散加权成像（DWI）和动态对比增强 MRI（DCE-MRI），获得多个序列，包括微血管通透性常数（K）。在治疗前后采集氟代脱氧葡萄糖微正电子发射断层扫描（(18)F-FDG 微 PET）。通过 MRI 测量肿瘤体积、增强比、坏死比、表观扩散系数（ADC）和 K，以及 FDG 微 PET 中的最大标准化摄取值（SUV(max)），将这些成像生物标志物与死后微血管造影和组织病理学相关联。
在 ZD6126 治疗组中，肿瘤生长较慢，48h 时坏死比例较高（P < 0.05），与组织病理学结果吻合；肿瘤 K 值从 1h 下降到 24h，48h 时部分恢复（P < 0.05），与增强比的变化一致（P < 0.05）；ADC 随肿瘤活力和灌注而变化；SUV(max)在 24h 时下降（P < 0.01）。48h 时肿瘤与肝脏的相对 K 值与微血管造影上的相对血管密度相关（r = 0.93，P < 0.05）。
这些成像生物标志物允许对血管关闭、坏死形成和肿瘤复发进行形态学、功能和代谢定量分析。单次 ZD6126 剂量可显著减少肿瘤血液供应和生长，直到治疗后 48h。
