PET IMAGING OF ESTROGEN RECEPTORS IN BREAST CANCER

乳腺癌对激素治疗的反应强烈影响 雌激素受体（ER）在肿瘤中的表达水平。目前， 原发性肿瘤的ER含量的测量用于乳腺癌 治疗选择这种方法受到ER异质性的限制 在肿瘤内和肿瘤部位之间表达。高达50%的患者 雌激素受体阳性的肿瘤对激素治疗没有反应。此外，委员会认为， 几乎所有患者最初对特定激素剂有反应， 最终会失败的治疗;但我们几乎没有洞察力的时间， 这种失败或对替代激素反应的可能性 剂. 本项目的总体目标是测量区域肿瘤ER含量 in vivo.我们假设我们可以预测对激素治疗的反应 通过使用PET成像对肿瘤雌激素结合进行非侵入性评估， [F18]-16 α-氟雌二醇（FES）。初步研究旨在制定 在各种乳腺癌患者中的定量成像方案， 完成了我们已经测试了定量雌激素结合的方法， 使用FES测量肿瘤，并发现FES测量之间具有良好的相关性， 初步患者ER摄取和定量免疫细胞化学 问题研究这种方法将应用于三个目标：（1） FES测量原发性和转移性肿瘤中ER含量的能力 肿瘤与活检标本的测定进行比较，（2）测量 大肿瘤患者ER表达的异质性和/或 多个病灶使用FES成像，并测试这些能力 用于预测对激素治疗的早期反应的测量，以及（3） 监测雌激素阻断程度和受体表达的变化 在他莫昔芬治疗过程中， 获得性抵抗除了患者研究，我们还将进行 FES转运和摄取到组织中实验室和动物研究， 完善我们对FES PET图像的分析。我们将测量FES与性的结合 类固醇结合蛋白（SBP）和FES及代谢物摄取到ER- 含有组织。 总之，我们将使用PET雌激素受体成像来回答基本的 关于乳腺癌ER生物学的问题。这将导致 在乳腺癌中使用激素治疗的显著改善 癌症，包括更好地选择患者进行激素治疗， 更好地决定何时以及如何改变那些 他莫昔芬治疗失败。

The response of breast cancer to hormonal therapy is strongly influenced by the level of estrogen receptor (ER) expression in the tumor. Currently, measures of the ER content of the primary tumor are used for breast cancer treatment selection. This approach is limited by heterogeneity of ER expression within tumors and between tumor sites. Up to 50% of patients with ER-positive tumors fail to respond to hormonal therapy. Furthermore, almost all patients initially responding to a particular hormonal agent will eventually fail therapy; but we have little insight to the timing of this failure or the likelihood of responding to alternative hormonal agents. The overall goal of this project is to measure regional tumor ER content in vivo. We hypothesize that we can predict response to hormonal therapy by non-invasive assessment of tumor estrogen binding using PET imaging and [F18]-16 alpha-fluoroestradiol (FES). Initial studies aimed at formulating quantitative imaging protocols in a variety of breast cancer patients have been completed. We have tested methods of quantifying estrogen binding in tumors using FES and have found good correlation between measures of FES uptake and quantitative ER immunocytochemistry in preliminary patient studies. This methodology will be applied to three aims: (1) Validate the ability the FES to measure ER content in both primary and metastatic tumors compared against assay of biopsy specimens, (2) Measure the heterogeneity of ER expression in patients with large tumors and/or multiple lesions using FES imaging and test the ability of these measurements to predict early response to hormonal therapy, and (3) Monitor the degree of estrogen blockade and changes in receptor expression over the course of tamoxifen therapy to identify potential mechanisms of acquired resistance. In addition to patient studies, we will perform laboratory and animal studies of FES transport and uptake into tissue to refine our analysis of FES PET images. We will measure FES binding to sex steroid binding protein (SBP) and FES and metabolite uptake into ER- containing tissue. In summary, we will use PET estrogen receptor imaging to answer basic question regarding the biology of the ER in breast cancer. This will lead to significant improvements in the use of hormonal therapy in breast cancer, including better selection of patients for hormonal therapy and better decisions on when and how the change therapy in those patients who fail tamoxifen therapy.