IN VIVO ASSESSMENT OF TUMOR RECEPTOR LEVELS USING PET

使用 PET 体内评估肿瘤受体水平

• 批准号: 2330763
• 负责人: FARROKH DEHDASHTI
• 金额: $ 26.85万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2330763
• 关键词: biopsy; breast neoplasm /cancer diagnosis; carcinoma; clinical research; deoxyglucose; estradiol; estrogen receptors; female; fluorine; glucose metabolism; hormone metabolism; hormone therapy; human subject; human therapy evaluation; longitudinal human study; neoplasm /cancer chemotherapy; positron emission tomography; prognosis; radionuclides; tamoxifen

Despite recent improvements in our understanding of the biology of breast cancer, few recent advances have been made in the systemic therapy of this disease, and present statistics indicate that 3.5% of American women will die of breast cancer. Initial treatment of advanced breast cancer is based on the hormone-receptor status of the tumor determined by in vitro assay for the ER in tumor tissue. Patients with advanced hormone- sensitive (ER+) cancer are treated by hormonal manipulation, and 55-60% of these women will respond favorably. Additional information is needed to predict response in individual patients more accurately, based on an in vivo functional assessment of estrogen receptor (ER) status and assessment of other factors predictive of tumor aggression; many such prognostic factors, including several nuclear proteins, have been evaluated, but none has currently proven more accurate than the status of the axillary nodes at diagnosis. In patients with metastatic ER+ disease who are treated with hormonal therapy, 7-10% will experience a symptomatic "flare reaction". This reaction has been attributed to the temporary agonist effect of the hormone and cannot be distinguished from disease progression clinically or radiologically, but is associated with subsequent response to that therapy. We have previously shown that positron emission tomography (PET) with 16alpha-[18F]fluoro-17beta-estradiol (FES) provides reliable in vivo information about the ER status of the tumor. Quantitative results of PET with [18F]-2-fluoro-2 deoxyglucose (FDG) have been shown by others to predict grade and behavior of several types of malignant tumors including breast cancer. We propose to perform serial PET with both FES and FDG and serial tumor biopsies (for assessment of several immunohistochemical prognostic factors) in women with locally advanced ER+ breast cancer before and early after initiation of tamoxifen therapy. It is expected that the combination of functional data provided by PET and that provided by prognostic-factor assessment will yield information about tumor aggression and hormonal sensitivity so that hormone therapy of advanced breast cancer can be individualized. We believe that a subclinical flare detected by PET imaging early after initiation of treatment may predict responsiveness to hormone therapy in this group of patients. Additionally, the results of this study should be translatable to patients with metastatic breast cancer and, hence, provide a method for distinguishing between the clinical flare reaction and disease progression.

尽管最近我们对乳腺生物学的理解有所提高， 癌症，很少有最近的进展，在系统治疗这一点 疾病，目前的统计数据表明，3.5%的美国妇女将 死于乳腺癌 晚期乳腺癌的早期治疗 基于通过体外测定的肿瘤的受体状态， 测定肿瘤组织中的ER。 激素水平高的病人- 敏感性（ER+）癌症通过激素操作治疗，55-60%的 这些女性会做出积极的回应。 需要更多的信息， 根据患者的临床表现， 雌激素受体（ER）状态的体内功能评估和评估 预测肿瘤侵袭性的其他因素;许多这样的预后 已经评估了包括几种核蛋白在内的因素，但没有一种 目前已被证明比腋窝淋巴结的状态更准确 在诊断。 接受治疗的转移性ER+疾病患者 使用激素治疗，7-10%的患者会出现症状性“发作 反应”。 这种反应归因于暂时性激动剂 激素的作用，不能与疾病进展区分开来 临床或放射学上，但与后续反应相关 接受治疗 我们以前已经证明，正电子发射 使用16 α-[18 F]氟-17 β-雌二醇（FES）进行断层扫描（PET）， 关于肿瘤ER状态的可靠体内信息。 用[18 F]-2-氟-2-脱氧葡萄糖（FDG）进行PET的定量结果表明， 被其他人证明可以预测几种类型的等级和行为。 恶性肿瘤包括乳腺癌。 我们建议用FES和FDG进行连续PET， 活检（用于评估几种免疫组化预后 因素）在局部晚期ER+乳腺癌妇女之前和早期 开始他莫昔芬治疗后。 预计该 PET提供的功能数据和 选择性因素评估将产生关于肿瘤侵袭性的信息 和激素敏感性，所以晚期乳腺癌的激素治疗 可以个性化。 我们认为，通过检测到的亚临床发作 治疗开始后早期的PET成像可以预测反应性 激素治疗的效果。 此外，结果 本研究的结论应可用于转移性乳腺癌患者 癌症，并因此提供了一种用于区分 临床发作反应和疾病进展。