TUMOR RESPONSE TO THERAPY CHARACTERIZED BY NMR

根据以下方面表征肿瘤治疗反应的研究 将进行代谢、血管和形态学变化， 确定肿瘤机制并建立潜在预测指标 控制和治疗。核磁共振波谱和成像 viva将作为非侵入性技术用于监测 高能磷酸盐代谢、血管分布和坏死 在接受选定的治疗方案的肿瘤中的发展。一个 体内肿瘤反应的评估是评价的期望目标 核磁共振提供了一种非侵入性的方法， 在同一组织内的反应的时间过程。 拟议的工作将集中在研究皮下的反应， 用光动力疗法（PDT）治疗的植入大鼠乳腺肿瘤。 磷核磁共振谱将用于高能磷酸盐的研究 代谢和pH值变化;氘NMR将用于跟踪吸收 作为肿瘤血流的测量;质子成像将是 用于监测和表征肿瘤坏死的发展; 和全氟化碳血液分布的氟成像 替代物将用于评估肿瘤的损伤程度 血管分布将应用局部光谱学和成像技术 以确定这些肿瘤的异质性治疗反应。代谢 以及组织区域的血管变化，其变得坏死，以及 将鉴定经历可逆代谢抑制的区域， 表征了肿瘤生长将在以下几周内监测： 治疗作为长期肿瘤控制的措施。相关性将是 在短期代谢、血管和形态学反应之间寻求 在PDT和长期肿瘤控制后， 机制，并询问核磁共振检测到的早期变化是否提供了 早期预测指标对后期肿瘤缓解的潜力。这些 结果将构成研究的基础，应用于其他选定的 实验肿瘤模型和治疗。

Studies to characterize therapeutic responses of tumors in terms of metabolic, vascular and morphologic changes will be carried out to help identify mechanisms and establish potential predictive indices for tumor control and cure. Nuclear Magnetic Resonance spectroscopy and imaging in viva will be used as noninvasive techniques to monitor the time course of changes in high energy phosphate metabolism, vascularity and necrotic development in tumors subjected to selected therapeutic regimens. An assessment of tumor response in vivo is a desired goal for the evaluation of cancer therapy and NMR provides a noninvasive means to follow in situ the time course of the response within the same tissue. The proposed work will focus on studying the response of subcutaneously implanted rat mammary tumors treated with photodynamic therapy, PDT. Phosphorus NMR spectroscopy will be used to study high energy phosphate metabolism and pH changes; deuterium NMR will be used to follow the uptake of D2O into tumors as a measure of tumor blood flow; proton imaging will be used to monitor and characterize the development of necrosis in the tumor; and fluorine imaging of the distribution of a perfluorocarbon blood substitute will be used to assess the extent of damage to tumor vascularity. Localized spectroscopy and imaging techniques will be applied to determine heterogeneous therapeutic responses in these tumors. Metabolic and vascular changes in regions of tissue, which become necrotic, and regions that undergo reversible metabolic inhibition will be identified and characterized. Tumor growth will be monitored over several weeks following treatment as a measure of long term tumor control. Correlations will be sought between short term metabolic, vascular and morphologic responses following PDT and long term tumor control to aid in the understanding of mechanisms and to ask whether early changes detected by NMR offer the potential of early predictive indices for later tumor response. These results will form the basis of studies to be applied to other selected experimental tumor models and therapies.