Beauregard D A, Thelwall P E, Chaplin D J, Hill S A, Adams G E, Brindle K M
Department of Biochemistry, University of Cambridge, UK.
Br J Cancer. 1998 Jun;77(11):1761-7. doi: 10.1038/bjc.1998.294.
The effects of combretastatin A4 prodrug on perfusion and the levels of 31P metabolites in an implanted murine tumour were investigated for 3 h after drug treatment using nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS). The area of regions of low signal intensity in spin-echo images of tumours increased slightly after treatment with the drug. These regions of low signal intensity corresponded to necrosis seen in histological sections, whereas the expanding regions surrounding them corresponded to haemorrhage. Tumour perfusion was assessed before and 160 min after drug treatment using dynamic MRI measurements of gadolinium diethylenetriaminepentaacetate (GdDTPA) uptake and washout. Perfusion decreased significantly in central regions of the tumour after treatment. This was attributed to disruption of the vasculature and was consistent with the haemorrhage seen in histological sections. The mean apparent diffusion coefficient of water within the tumour did not change, indicating that there was no expansion of necrotic regions during the 3 h after drug treatment. Localized 31P-MRS showed that there was decline in cellular energy status in the tumour after treatment with the drug. The concentrations of nucleoside triphosphates within the tumour fell, the inorganic phosphate concentration increased and there was a significant decrease in tumour pH for 80 min after drug treatment. The rapid, selective and extensive damage caused to these tumours by combretastatin A4 prodrug has highlighted the potential of the agent as a novel cancer chemotherapeutic agent. We have shown that the response of tumours to treatment with the drug may be monitored non-invasively using MRI and MRS experiments that are appropriate for use in a clinical setting.
使用核磁共振成像（MRI）和光谱学（MRS）研究了秋水仙素A4前药对植入小鼠肿瘤的灌注及31P代谢物水平的影响，药物处理后观察3小时。药物处理后，肿瘤自旋回波图像中低信号强度区域的面积略有增加。这些低信号强度区域对应于组织学切片中所见的坏死区域，而其周围扩大的区域对应于出血。使用钆二乙三胺五乙酸（GdDTPA）摄取和洗脱的动态MRI测量评估药物处理前和处理后160分钟的肿瘤灌注。处理后肿瘤中心区域的灌注显著降低。这归因于脉管系统的破坏，并且与组织学切片中所见的出血一致。肿瘤内水的平均表观扩散系数未改变，表明在药物处理后的3小时内坏死区域没有扩大。局部31P-MRS显示药物处理后肿瘤细胞能量状态下降。肿瘤内三磷酸核苷浓度降低，无机磷酸盐浓度升高，药物处理后80分钟肿瘤pH值显著下降。秋水仙素A4前药对这些肿瘤造成的快速、选择性和广泛损伤突出了该药物作为新型癌症化疗药物的潜力。我们已经表明，可以使用适用于临床环境的MRI和MRS实验对肿瘤对该药物治疗的反应进行无创监测。
