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Correlative Study on Abnormal Tumor Vascularity and Metabolism

肿瘤血管异常与代谢的相关性研究

基本信息

批准号：
01480271
负责人：
ISHII Yasushi
金额：
$ 3.9万
依托单位：
Fukui Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

Recent progress of the imaging diagnosis has already established to detect the existence of tumor and its degree of extension. However, in order to select and evaluate the adequate therapeutic regimen, further specified information characterized by physiological state of the tumor such as perfusion and metabolic state should be known. On this line, to understand physiological environment of the tumor as a mass of tumor cells, correlative studies on abnormal vascurality and high enagy metabolism were perfomed at present. A series bf tumor bearing nude mice were subjected to examine using MR contrast enhancement study as well as hydrogen clearance method to evaluate perfusion status, and ^<31>P or ^<>H MR spectroscopy (MRS) to evaluate energetic metabolism. These physiological parameters of the tumor insitu were observed during tumor growth and after therapeutic intervention such as radiation and hyperthermia. During tumor growth, tumor perfusion became insufficient and resulted in anerobic metabolic state oh the whole, and these were improved by irradiation as has been hypothesized by rexygenation process. However, after application of hyperthermia, complete ischemia consequent with metabolic decline were induced. Combined application of these two intervention with opposite effect on the tumor, namely, metabolic activation or decline, revealed additive effect without cancellation, each other. Thus, present result indicated that a growing tumor became heterogenous composing of different perfusion state with different metabolic state, and, therefore, different therapeutic intervention was necessary to induce additive effect on the whole. Futher investigation concerning tumor heterogeneity on the ground of macropathology should be necessary to establish adequate selection of therapeutic intervention. On this line, noninvasive imaging of metabolites such as chemical shift imaging (CSI) using clinical MRI should be completed as a next step.

影像学诊断的最新进展已经确立了检测肿瘤的存在及其扩展程度。然而，为了选择和评估适当的治疗方案，应该知道以肿瘤的生理状态为特征的进一步指定的信息，例如灌注和代谢状态。在此基础上，为了更好地了解肿瘤作为肿瘤细胞团的生理环境，目前对肿瘤血管异常和高能量代谢进行了相关研究。采用MR对比增强技术和氢清除法评价荷瘤裸鼠脑组织灌注状态，用~ <31>1H-P或~ 1H-MRS评价荷瘤裸鼠脑组织能量代谢。在肿瘤生长过程中和治疗干预（如放射和热疗）后原位观察肿瘤的这些生理参数。在肿瘤生长过程中，肿瘤灌注变得不足，导致整体上处于无氧代谢状态，并且如再氧过程所假设的那样，这些通过照射得到改善。然而，应用高温后，完全缺血随之而来的代谢下降。联合应用这两种对肿瘤具有相反作用的干预措施，即代谢活化或下降，显示了相互不抵消的累加效应。因此，目前的结果表明，生长中的肿瘤成为异质性组成的不同灌注状态与不同的代谢状态，因此，不同的治疗干预是必要的，以诱导整体上的累加效应。在宏观病理学的基础上进一步研究肿瘤异质性对于建立适当的治疗干预措施是必要的。在这条线上，代谢物的非侵入性成像，如化学位移成像（CSI）使用临床MRI应作为下一步完成。