PET IMAGING OF ESTROGEN RECEPTORS IN BREAST CANCER

乳腺癌对激素治疗的反应受到强烈影响。 通过雌激素受体(ER)在肿瘤中的表达水平。目前， 乳腺癌原发灶ER含量的测定方法 治疗选择。这种方法受到内质网异质性的限制 在肿瘤内和肿瘤部位之间的表达。高达50%的患者 雌激素受体阳性的肿瘤对激素治疗无效。此外， 几乎所有患者最初对一种特定的激素剂有反应 最终会导致治疗失败；但我们对治疗的时机知之甚少 这种失败或对替代激素反应的可能性 探员们。 该项目的总体目标是测量局部肿瘤ER含量 在活体内。我们假设我们可以预测对激素治疗的反应 通过使用PET成像和无创评估肿瘤雌激素结合 [F18]-16α-氟雌醇(FES)。初步研究旨在制定 各种乳腺癌患者的定量成像方案 已经完成了。我们已经测试了量化雌激素结合的方法 FES与肿瘤的FES指标之间存在良好的相关性 初诊患者摄取和定量ER免疫细胞化学 学习。这一方法将应用于三个目标：(1)验证 FES测定原发灶和转移灶ER含量的能力 肿瘤与活检标本化验的比较，(2)测量 大肿瘤和/或大肿瘤患者ER表达的异质性 使用FES成像检查多个病变并测试这些功能 预测激素治疗早期反应的测量方法，以及(3) 监测雌激素的阻断程度和受体表达的变化 在他莫昔芬治疗过程中，以确定潜在的机制 后天抵抗力。除了患者研究，我们还将进行 FeS在组织中转运和摄取的实验室和动物研究 改进我们对FES PET图像的分析。我们将测量FES与性的结合 内质网摄取类固醇结合蛋白(SBP)和FES及代谢物 含有组织的。 总之，我们将使用PET雌激素受体成像来回答基本问题 关于乳腺癌ER生物学的问题。这将导致 荷尔蒙治疗在乳房的应用有了显著的改善 癌症，包括更好地选择患者进行激素治疗和 更好地决定改变治疗的时间和方式 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.