Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging
Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging
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DOI：
10.1200/jco.2002.09.144
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发表时间：
2002-09-15
影响因子：
45.3
通讯作者：
Padhani, AR
中科院分区：
文献类型：
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作者：
Galbraith, SM;Rustin, GJS;Padhani, AR
目的：5，6-二甲基氧杂蒽酮-4-乙酸（DMXAA）在临床前模型中导致血管关闭。动态对比增强（DCE）磁共振成像（MRI）研究在I期试验中进行，以检查肿瘤和肌肉中与血流和渗透性相关的变化。患者和方法：16例患者接受DMXAA治疗，剂量为500 - 4，900 mg/m2，治疗前后进行DCE-MRI检查。计算肌肉和肿瘤中感兴趣区域（ROI）中每个像素的最大梯度、最大增强和前90秒的信号强度时间曲线下面积（AUC），并获得每个ROI的中值。治疗后的变化进行了比较，95%的限制，一个人的协议，并为集团使用数据从我们的reproducibility study.Results：9 16例患者有显着减少的AUC 24小时后，第一次剂量的DMXAA，和8 11例患者减少了高达66%的AUC 24小时后，最后一次剂量。末次给药后24小时，梯度、增强和AUC的平均降低分别为25%、18%和31%，显著大于一组11例患者的95%变化限度。第一次给药后24小时肌肉中的增强和AUC显著降低，但在最后一次给药后24小时未见显著变化。结论：DMXAA在较宽的剂量范围内显著降低与肿瘤血流相关的DCE-MRI参数，与报道的肿瘤血管靶向活性一致。DMXAA的进一步临床评价是必要的。(C)2002年，美国临床肿瘤学会。
PurposE: 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) causes vascular shutdown in preclinical models. Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) studies were performed in the phase I trials to examine changes related to blood flow and permeability in tumor and muscle.Patients and Methods: Sixteen patients treated with DMXAA from 500 to 4,900 mg/m(2) had DCE-MRI examinations before and after treatment. The maximum gradient, the maximum enhancement, and the area under the signal-intensity-time curve (AUC) over the first 90 seconds were calculated for each pixel in regions of interest (ROIs) in muscle and tumor, and the median value for each ROI was obtained. Changes after treatment were compared with 95% limits of agreement for an individual and for groups using data from our reproducibility study.Results: Nine of 16 patients had significant reductions in AUC 24 hours after the first dose of DMXAA, and eight of 11 patients had reductions of up to 66% in AUC 24 hours after the last dose. Mean reductions in gradient, enhancement, and AUC were 25%, 18%, and 31%, respectively, 24 hours after the last dose, significantly greater than the 95% limits of change for a group of 11 patients. Enhancement and AUC in muscle 24 hours after the first dose were significantly reduced, but no significant changes were seen 24 hours after the last dose.Conclusion: DMXAA significantly reduces DCE-MRI parameters related to tumor blood flow, over a wide dose range, consistent with the reported tumor vascular targeting activity. Further clinical evaluation of DMXAA is warranted. (C) 2002 by American Society of Clinical Oncology.