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

描述（由申请人提供）：在前列腺癌转移性骨病患者中，骨吸收和骨形成标志物升高与严重骨骼问题、疾病进展和死亡风险增加显著相关。不幸的是，骨代谢的生物标志物对于常规临床使用不够敏感或选择性，仅提供粗略的风险分层。我们建议将骨转换的预后价值应用于个体患者，通过验证一种新的方法来高精度评估50例前列腺癌骨转移患者的骨转换。我们的建议涉及永久标记这些人与一个单一的小口服剂量的罕见（但很容易产生）的41钙同位素，与可忽略不计的终身放射性41暴露。在18个月的观察期内定期测量小尿液样本中的41Ca丰度将能够准确评估骨转换以及对其变化的方便的长期监测，并且具有前所未有的灵敏度。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。我们假设，利用加速器质谱法进行的尿41 Ca测定将有助于风险评估、疾病分期、治疗效果的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，最大限度地减少晚期前列腺癌的破坏性后果，从而提高患者的生活质量和生存预期。最终，经过验证的41Ca检测也可用于早期转移性扩散的检测和研究，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性测试。

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.