Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C magnetic resonance spectroscopy.
Detection of tumor response to a vascular disrupting agent by hyperpolarized 13C magnetic resonance spectroscopy.
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DOI：
10.1158/1535-7163.mct-10-0706
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发表时间：
2010-12
影响因子：
5.7
通讯作者：
Brindle KM
中科院分区：
文献类型：
--
作者：
Bohndiek SE;Kettunen MI;Hu DE;Witney TH;Kennedy BW;Gallagher FA;Brindle KM
核自旋超极化可以显着增加13 C磁共振实验的灵敏度，允许动态测量超极化13 C标记底物在体内的代谢。在这里，我们报告了淋巴瘤肿瘤对血管破坏剂考布他汀-A4-磷酸的反应的临床前研究，通过测量超极化[1- 13 C]丙酮酸和[1，4 - 13 C2]富马酸的肿瘤代谢变化来检测。这些测量结果与动态对比剂增强磁共振成像（DCE-MRI）测量肿瘤血管功能和扩散加权MRI（DW-MRI）测量肿瘤细胞坏死，导致随后的肿瘤灌注损失进行了比较。描述[1- 13 C]丙酮酸和乳酸之间超极化13 C标记通量的速率常数在考布他汀-A4-磷酸处理6小时内降低34%，并在24小时保持在该较低水平。描述超极化[1，4 - 13 C2]富马酸盐产生标记苹果酸的速率常数在处理后6小时和24小时分别增加1.6倍和2.5倍，并与组织学切片中检测到的坏死程度相关。DCE-MRI测量显示治疗后6小时灌注显著减少，24小时恢复，扩散加权成像显示治疗后6小时肿瘤水的表观扩散系数无变化，尽管在24小时增加了32%（p<0.02），组织学观察到广泛坏死区域。因此，与DCE或DW-MRI相比，超极化[1- 13 C]丙酮酸盐和[1，4 - 13 C2]富马酸盐代谢的测量可分别提供对血管干扰剂反应的更持续和更灵敏的指标。
Nuclear spin hyperpolarization can increase dramatically the sensitivity of the 13C magnetic resonance experiment, allowing dynamic measurements of the metabolism of hyperpolarized 13C-labeled substrates in vivo. Here, we report a preclinical study of the response of lymphoma tumors to the vascular disrupting agent, combretastatin-A4-phosphate, as detected by measuring changes in tumor metabolism of hyperpolarized [1-13C]pyruvate and [1,4-13C2]fumarate. These measurements were compared with dynamic contrast agent enhanced magnetic resonance imaging (DCE-MRI) measurements of tumor vascular function and diffusion-weighted MRI (DW-MRI) measurements of the tumor cell necrosis that resulted from subsequent loss of tumor perfusion. The rate constant describing flux of hyperpolarized 13C label between [1-13C]pyruvate and lactate was decreased by 34% within 6 h of combretastatin-A4-phosphate treatment and remained at this lower level at 24 h. The rate constant describing production of labeled malate from hyperpolarized [1,4-13C2]fumarate increased 1.6-fold and 2.5-fold at 6 and 24 h after treatment respectively and correlated with the degree of necrosis detected in histological sections. While DCE-MRI measurements showed a substantial reduction in perfusion at 6 h after treatment, which had recovered by 24 h, diffusion-weighted imaging showed no change in the apparent diffusion coefficient of tumor water at 6 h after treatment, although there was a 32% increase at 24 h (p<0.02), when regions of extensive necrosis were observed by histology. Measurements of hyperpolarized [1-13C]pyruvate and [1,4-13C2]fumarate metabolism may provide therefore a more sustained and sensitive indicator of response to a vascular disrupting agent than DCE-or DW-MRI respectively.