A simple urinary assay for sensitive prognosis of disease progression and death f

描述(申请人提供)：在前列腺癌转移性骨疾病患者中，骨吸收和形成标志物的升高与严重骨骼问题、疾病进展和死亡的风险增加显著相关。不幸的是，骨代谢的生物标志物对于常规的临床应用不够敏感或选择性，只能提供粗略的风险分层。通过验证一种高精度评估50例前列腺癌骨转移患者骨转换的新方法，我们建议将骨转换的预后价值应用于个体患者。我们的建议包括给这些人永久地贴上一小剂量口服稀有(但容易生产)的41Ca同位素的标签，终身接触的放射性41可以忽略不计。在18个月的观察期内定期测量小量尿样中的41Ca丰度，将能够准确地评估骨转换，并以前所未有的灵敏度方便地长期监测其变化。为了评估这种新方法的最终效用，基于41Ca的骨转换测量将与晚期前列腺癌的疾病结局和标准医学诊断技术相关联。我们推测，利用加速器质谱仪进行尿41Ca测定将有助于风险评估、疾病分期、疗效测量和进行性骨病的灵敏检测。我们提出的工作的总体目标是将一种新的、安全的、非侵入性的、准确的、高精度的骨转换评估方法转化为临床工具，为肿瘤学家提供一种新的定量测量癌症引起的骨骼代谢变化的方法。该项目的直接好处将是通过更有效的患者护理将晚期前列腺癌的破坏性后果降至最低，从而改善患者的生活质量和生存预期。最终，经过验证的41Ca检测在检测和研究早期转移扩散方面也可能有用，从而能够对旨在预防这种灾难性疾病状态的治疗进行系统测试。

DESCRIPTION (provided by applicant): In patients with metastatic bone disease from prostate cancer, elevated markers of bone resorption and formation are significantly associated with increased risk of severe skeletal problems, disease progression, and death. Unfortunately, biomarkers of bone metabolism are not sensitive or selective enough for routine clinical use, providing only coarse risk stratification. We propose to apply the prognostic value of bone turnover to individual patients, by validating a novel method for high precision assessment of bone turnover in 50 prostate cancer patients with bony metastasis. Our proposal involves permanently labeling these individuals with a single small oral dose of the rare (but easily produced) 41Ca isotope, with negligible lifetime radioactive 41 exposure. Regular measurement of 41Ca abundance in small urine specimens over an 18 month observation period will enable an accurate assessment of bone turnover as well as a convenient long-term monitor of changes thereof, and at unprecedented sensitivity. In order to assess the ultimate utility of this novel method, 41Ca-based bone turnover measurements will be correlated with disease outcome and standard medical diagnostic techniques for advanced prostate cancer. We hypothesize that a urinary 41Ca assay utilizing accelerator mass spectrometry will be useful for risk assessment, disease staging, measurement of therapeutic efficacy, and sensitive detection of progressive bony disease. Our general goal for the proposed work is to translate a novel, safe, non-invasive, accurate, high precision method for bone turnover assessment into a clinical tool, providing oncologists with a new quantitative measure of cancer-induced changes in skeletal metabolism. Direct benefits of this project will be in minimizing the devastating consequences of late stage prostate cancer through more effective patient care, thereby improving patient quality of life and survival expectations. Ultimately, a validated 41Ca assay could also be useful in the detection and study of early metastatic spread, enabling systematic testing of therapies aimed at preventing this catastrophic disease state.