Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy
Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy
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DOI：
10.1200/jco.2005.07.144
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发表时间：
2005-06-20
影响因子：
45.3
通讯作者：
Lawrence, TS
中科院分区：
文献类型：
--
作者：
Cao, Y;Tsien, CL;Lawrence, TS
目的：为了使化疗与放疗对高级别胶质瘤产生协同和安全的作用，药物必须通过血瘤屏障（BTB）的内皮连接到达所有肿瘤细胞，而不能通过血脑屏障（BBB）对正常脑产生毒性。本研究的目的是在高级别胶质瘤放疗过程中使用磁共振成像（MRI）评估BBB/BTB状态。患者与方法16例接受适形放疗（RT）的3级或4级幕上恶性胶质瘤患者在放疗前、放疗中、放疗结束后分别行MRI增强扫描，分析钆二乙烯三胺五乙酸（Gd-DTPA）摄取指数与肿瘤及放疗剂量的关系。结果在非增强肿瘤区，造影剂摄取在约10 Gy后显著增加（P < 0.01），在约30 Gy后达到最大值。在最初增强造影剂的肿瘤区域，造影剂摄取在放疗过程中下降，在没有进展性疾病的患者完成放疗后变得显著。在照射期间和照射后，健康的大脑仅显示不显著的变化。结论MRI造影显示，在放疗过程中，Gd-DTPA摄取在最初未增强的肿瘤区域增加，而在其余脑区没有增加，提示BTB打开。这一发现表明适形放疗对BTB的影响比对血脑屏障的影响更具选择性，并且可能存在一个窗口，从放疗开始后1周到治疗完成后1个月，在此期间药物可最大限度地进入高级别胶质瘤。
Purpose For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas.Patients and Methods Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received.Results In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation.Conclusion Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to I month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.