MRI AND MRS OF HORMONAL INDUCED CHANGES IN BREAST CANCER

这项研究的长期目标是开发一种非侵入性的 早期评估乳腺癌反应的方法 使用磁共振成像的方法对患者进行激素治疗 (MRI)光谱学（MRS）该提案将侧重于体内MRI， 人乳腺癌植入物（例如，MCF 7、T47 D和MDA-MB-1）的MRS研究 231细胞系）在生长期间和用 抗雌激素药（例如他莫昔芬，ICI 182780）。 所提出的实验旨在检验我们的假设， 他莫昔芬抑制雌激素刺激的血管生成生长 影响并损害血管系统的功能，从而导致 坏死增强。 肿瘤内皮细胞的近期组织化学染色 细胞支持这一假设。 内皮细胞染色也 表明刺激内皮细胞生长的边界， 坏死和存活的肿瘤细胞区域。 这些边界毛细血管 似乎在T1加权，动态， 增强MR图像。 鉴于这一系列事件，我们 建议集中在以下三个领域，预计这些领域将 揭示肿瘤对抗雌激素的反应： 1.大体组织病理学特征的表征（例如坏死， 纤维化），在生长期间和生长过程中通过MRI以高空间分辨率获得。 治疗过程这部分要求与以下内容准确关联： 组织病理学结果。 2.肿瘤的分布、功能和完整性研究 在生长过程中和治疗后的血管。这一部分将包括 在高时间和空间分辨率下使用动态对比增强MRI， 分辨率以及与免疫组化研究的相关性， 微血管和内皮细胞。 3.监测葡萄糖的输送和代谢以及 在生长和治疗过程中乳酸的产生和清除。在这些 我们计划利用13 C标记的葡萄糖进行空间测量， 定义了高时间分辨率的13 C MRS和13 C-1H检测方法。 为了建立时间的相关性之间的积累， 抗雌激素及其产品和增强的抗雌激素及其产品的作用 我们建议在本项目中纳入19 F药代动力学研究 他莫昔芬和ICI 182780的氟化衍生物。

The long range objective of this research is to develop a non-invasive procedure for the early evaluation of the response of breast cancer patients to hormonal therapy, using methods of magnetic resonance imaging (MRI) and spectroscopy (MRS). This proposal will focus on in vivo MRI and MRS studies of human breast cancer implants (e.g. MCF7, T47D and MDA-MB- 231 cell lines) in nude mice during growth and following treatment with antiestrogens (e.g. tamoxifen, ICI 182780). The proposed experiments were designed to test our hypothesis that tamoxifen inhibits estrogen stimulated production of angiogenic growth factors and impairs the function of the vascular system thereby causing enhanced necrosis. Recent histochemical staining of the tumor endothelial cells lended support to this hypothesis. The endothelial staining also indicated stimulation of endothelial growth at the boundary of the necrotic and viable tumor cells regions. These boundary capillaries appeared to exhibit high permeability in the T1 weighted, dynamic, contrast enhanced MR images. In view of this sequence of events we propose to concentrate on the following three areas which are expected to reveal the tumor response to antiestrogens: 1. Characterization of gross histopathological features (e.g. necrosis, fibrosis) obtained by MRI at high spatial resolution during growth and in the course of therapy. This part requires an accurate correlation with histopathological findings. 2. Study of the distribution, functionality and integrity of the tumor vasculature during growth and following treatment. This part will include the use of dynamic, contrast enhanced MRI at high temporal and spatial resolution as well as correlation with immunohistochemical studies of the microvessels and endothelial cells. 3. Monitor the delivery and metabolism of glucose as well as the production and clearance of lactate during growth and therapy. In these measurements we plan to utilize 13C labeled glucose and to apply spatially defined 13C MRS and 13C-1H-detected methods at high temporal resolution. In order to establish the time correlation between the accumulation of the antiestrogen and its products and response to its action by enhanced necrosis we propose to include in this project 19F pharmacokinetic studies of the fluorinated derivatives of tamoxifen and ICI 182780.