DETERMINATION OF ESTROGEN RECEPTOR CONTENT IN BREAST CANCER BY PET

乳腺癌的治疗和预后在很大程度上取决于 雌激素受体的肿瘤含量。有高水平的患者 雌激素受体对激素药物的治疗有反应 比接受雌激素受体的患者有更长的无病间隔 阴性肿瘤。当患者表现为原发性乳腺癌时， 治疗是基于切除后确定的雌激素受体水平。 肿瘤组织。宠物成像提供了使 两种动物体内雌激素受体含量的测定 播散性疾病。 我们将检验这样一种假设，即乳房的雌激素受体含量 使用[F-18]的PET成像可以在体内确定癌症 氟雌二醇。在原发肿瘤患者中，[F-18]摄取 表示为每克注射剂量的百分比将被关联 切除的组织上雌激素受体密度独立确定 采用放射免疫分析和免疫细胞化学方法。我们还将评估 乳腺癌患者转移率的局部变异 雌激素受体的表达。因为不同的转移部位 对激素治疗的不同反应，一年中多达三个部位 将对个别患者进行研究。[F-18]氟雌二醇的摄取 将与对激素治疗的反应逐一相关 基础。在同一组患者中，我们将观察[F-18]的变化 当患者接受激素治疗时，随着时间的推移雌激素的摄取 心理治疗。肿瘤雌激素受体含量将与时间相关 在现场的基础上对疾病的进展进行监测。 我们还将合成几种新的[F-18]雌二醇 旨在降低受体部位新陈代谢的特征 减少非靶组织的摄取。新合成的 放射性药物的结合特性将在 利用人类子宫组织进行生物测定。靶区和靶区生物分布 非靶组织将在年轻的雌性Spraogue-Dawley大鼠身上进行评估。 当临床前评估完成后，我们将执行Complete 乳腺癌患者的生物分布研究以评估这些 适用于正电子发射计算机断层扫描的各种雌二醇。生物分布 研究还将包括对患者系列血液样本的分析 活性代谢物的存在。当患者的生物分布研究 [F-18]摄取与放射免疫测定有良好的相关性 测定肿瘤雌激素水平时，我们会使用患者衍生的 结合体外结合亲和力的生物分布数据 用间隔法测定雌激素受体的绝对含量 受体系统的模型。

Treatment and prognosis of breast cancer is dependent in large part on the tumor content of estrogen receptor. Patients who have high levels of estrogen receptor will respond to treatment with hormonal agents and have a longer disease free interval than patients with estrogen receptor negative tumor. When a patient presents with primary breast cancer, treatment is based on estrogen receptor level determined on resected tumor tissue. PET imaging offers the capability of making the determination of estrogen receptor content in vivo in both primary and disseminated disease. We will test the hypothesis that the estrogen receptor content of breast cancers can be determined in vivo with PET imaging using [F-18] fluoroestradiols. In patients with primary tumors, [F-18] uptake expressed as the percent of the injected dose per gram will be correlated with estrogen receptor density determined on excised tissue independently by radioimmunoassay and immunocytochemistry. We will also evaluate metastases in breast cancer patients for site-to-site variation in estrogen receptor expression. Because separate metastatic sites have variable responses to hormonal therapy, up to three sites in an individual patient will be studied. Uptake of [F-18] fluoroestradiol will be correlated with response to hormonal therapy on a site by site basis. In the same group of patients, we will observe changes in [F-18] estradiol uptake over time while the patient is receiving hormonal therapy. Tumor estrogen receptor content will be correlated with time to progression of disease on a sit-by-site basis. We will also synthesize several new [F-18] estradiols with characteristics designed to reduce metabolism at the receptor site and reduce uptake in non-target tissues. Newly synthesized radiopharmaceuticals will be evaluated for binding characteristics in a bioassay utilizing human uterus tissue. Biodistribution in target and non-target tissues will be evaluated in young female Sprague-Dawley rats. When pre-clinical evaluations are completed, we will perform complete biodistribution studies in breast cancer patients to evaluate these various estradiols for suitability for PET imaging. Biodistribution studies will also include analysis of patient serial blood samples for the presence of active metabolites. When patient biodistribution studies show good correlation of [F-18] uptake with radioimmune assay determination of tumor estrogen level, we will use the patient derived biodistribution data in combination with in vitro binding affinity values to determine absolute estrogen receptor content using compartmental models for receptor systems.