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在钆喷酸葡胺-丁二酸单甲酯(Gd-DTPA-BMA)存在的情况下体外检测凋亡细胞死亡。

Detection of apoptotic cell death in vitro in the presence of Gd-DTPA-BMA.

作者信息

Bailey Colleen, Giles Anoja, Czarnota Gregory J, Stanisz Greg J

机构信息

Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

出版信息

Magn Reson Med. 2009 Jul;62(1):46-55. doi: 10.1002/mrm.21972.

DOI:10.1002/mrm.21972
PMID:19253383
Abstract

Due to variability in patient response to cancer therapy, there is a growing interest in monitoring patient progress during treatment. Apoptotic cell death is one early marker of tumor response to treatment. Using known extracellular concentrations of gadolinium diethylenetriamine pentaacetic acid bismethylamide (Gd-DTPA-BMA) to vary the exchange regime, T(1) and T(2) relaxation data for acute myeloid leukemia (AML) cell samples were obtained and then analyzed using a two-pool model of relaxation with exchange. Leukemia cells treated with cisplatin to induce apoptosis exhibited a statistically significant (P < 0.05) decrease in intracellular longitudinal relaxation time, T(1I), from 1030 ms to 940 ms, a decrease (P < 0.001) in the intracellular water fraction, M(0I), from 0.86 to 0.68 and a statistically significant increase (P < 0.01) in transmembrane water exchange rate, k(IE), from 1.4 s(-1) to 6.8 s(-1). The changes in MR parameters correlated with quantitative histology, such as cellular cross-sectional area and average nuclear area measurements. The results of this study emphasize the importance of accounting for water exchange in dynamic contrast-enhanced MRI (DCE-MRI) studies, particularly those that examine tumor response to therapies in which apoptotic changes occur.

摘要

由于患者对癌症治疗的反应存在差异,在治疗过程中监测患者进展的兴趣日益浓厚。凋亡性细胞死亡是肿瘤对治疗反应的一个早期标志物。利用已知的细胞外钆二乙三胺五乙酸双甲酰胺(Gd-DTPA-BMA)浓度来改变交换机制,获得了急性髓系白血病(AML)细胞样本的T(1)和T(2)弛豫数据,然后使用带有交换的双池弛豫模型进行分析。用顺铂处理以诱导凋亡的白血病细胞,其细胞内纵向弛豫时间T(1I)从1030毫秒显著下降(P < 0.05)至940毫秒,细胞内水分数M(0I)从0.86下降(P < 0.001)至0.68,跨膜水交换率k(IE)从1.4 s(-1)显著增加(P < 0.01)至6.8 s(-1)。磁共振参数的变化与定量组织学相关,如细胞横截面积和平均核面积测量。本研究结果强调了在动态对比增强磁共振成像(DCE-MRI)研究中考虑水交换的重要性,特别是那些检查肿瘤对发生凋亡变化的治疗反应的研究。

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