Does Arterial Spin-labeling MR Imaging-measured Tumor Perfusion Correlate with Renal Cell Cancer Response to Antiangiogenic Therapy in a Mouse Model?
Does Arterial Spin-labeling MR Imaging-measured Tumor Perfusion Correlate with Renal Cell Cancer Response to Antiangiogenic Therapy in a Mouse Model?
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DOI：
10.1148/radiol.2521081059
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发表时间：
2009-06-01
期刊：
影响因子：
19.7
通讯作者：
Goldberg, S. Nahum
中科院分区：
文献类型：
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作者：
Schor-Bardach, Rachel;Alsop, David C.;Goldberg, S. Nahum
目的：确定动脉自旋标记（ASL）磁共振（MR）成像在基线和抗血管生成治疗早期的发现是否可以预测后期对治疗的抵抗。材料和方法：方案经机构动物护理和使用委员会批准。将Caki-1、A498和786-0人肾细胞癌异种移植物植入39只裸鼠体内。一旦肿瘤达到12毫米，动物每公斤体重接受80毫克索拉非尼，每天一次。在基线和第14天进行ASL成像，786-0和A498（3天至12周）进行额外成像。分析平均血流量值和血流量空间分布的定性差异，并与组织病理学结果进行活力和微血管密度的比较。采用t检验比较肿瘤平均血流量的差异。Bonferroni-adjusted P值小于。0.05表示差异显著。结果：A498的基线血流量为80.1 mL/ 100g /min +/- 23.3（标准差），786-0的基线血流量为75.1 mL/ 100g /min +/- 28.6， Caki-1的基线血流量为10.2 mL/ 100g /min +/- 9.0。Caki-1处理后的流量无显著变化（14.9 mL/100 g/min +/- 7.6），而A498处理后的流量在第14天（47.9 mL/100 g/min +/- 21.1）和786-0处理后的第3天（20.3 mL/100 g/min +/- 8.7）均下降（P = 0.003和P = 0.003）。分别为03)。对于A498，在接受索拉非尼的28-42天测得最低值。血流增加的区域发生在肿瘤生长前35-49天、17-32天以及平均血流显著增加前（第77天）。尽管786-0在组织病理学检查中显示了新的进展性区域，其信号强度早在第5天就被检测到，与存活的肿瘤相关，但在第3天与随后的所有天相比，平均流量没有明显变化（P < 0.05）。结论：ASL成像提供了对索拉非尼有反应的RCC系肿瘤生存能力的临床相关信息。(c) rsna， 2009年
Purpose: To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic therapy can predict later resistance to therapy.Materials and Methods: Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma (RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498 (3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences.Results: Baseline blood flow was 80.1 mL/100 g/min +/- 23.3 (standard deviation) for A498, 75.1 mL/100 g/min +/- 28.6 for 786-0, and 10.2 mL/100 g/min +/- 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min +/- 7.6) in flow, whereas flow decreased in all treated A498 on day 14 (47.9 mL/100 g/min +/- 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min +/- 8.7) (P = .003 and .03, respectively). For A498, lowest values were measured at 28-42 days of receiving sorafenib. Regions of increased flow occurred on days 35-49, 17-32 days before documented tumor growth and before significant increases in mean flow (day 77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent days (P > .99).Conclusion: ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib. (C) RSNA, 2009