Image Biomarker Development for TreatmentEfficacy of Prostate Cancer to the Bone

图像生物标志物的开发用于前列腺癌骨的治疗效果

• 批准号: 8192925
• 负责人: Brian D. Ross
• 金额: $ 51.54万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-21 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8192925
• 关键词: Adopted; Androgens; Angiogenesis Inhibitors; Animals; Apoptosis; Biological Markers; Bioluminescence; Cancer Model; Cancer Patient; Caspase; Cell Death; Cell Density; Cell membrane; Cilengitide; Clinic; Clinical; Clinical Research; Clinical Trials; Combined Modality Therapy; Consensus; Cytotoxic Chemotherapy; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic radiologic examination; Diffusion; Diffusion Magnetic Resonance Imaging; Drug Approval; Drug Delivery Systems; Early Diagnosis; Early treatment; Effectiveness; Environment; Epidermal Growth Factor Receptor; Evaluation; Foundations; Goals; Health; Human; Image; In Vitro; Investments; Ionizing radiation; Lesion; Magnetic Resonance Imaging; Malignant Bone Neoplasm; Malignant Neoplasms; Malignant neoplasm of prostate; Maps; Measurement; Metastatic Neoplasm to the Bone; Metastatic Prostate Cancer; Methods; Modality; Molecular; Monitor; Motion; Mus; Neoplasm Metastasis; Oncogenic; Oncologist; Outcome; Outcome Assessment; Outcome Measure; PC3 cell line; Patient Care; Patients; Pharmaceutical Preparations; Phase II Clinical Trials; Phase III Clinical Trials; Positron-Emission Tomography; Process; Prostate; Public Health; Radionuclide Imaging; Reporter; Research; Resistance; Signal Pathway; Signal Transduction; Site; System; Systemic Therapy; Therapeutic; Therapeutic Intervention; Treatment Failure; Tumor Burden; Tumor Tissue; Tumor-Derived; Tumorigenicity; Validation; Water; X-Ray Computed Tomography; base; bone; cancer cell; cancer therapy; chemotherapy; cytotoxic; deprivation; design; docetaxel; extracellular; molecular imaging; mouse model; neoplastic cell; novel; quantum; radiologist; residence; response; response marker; single photon emission computed tomography; skeletal; therapy resistant; treatment response; tumor; water diffusion

DESCRIPTION (provided by applicant): The treatment of oncogenic lesions residing in bone has advanced with an ever increasing array of therapies; however, response to treatment is considered "unmeasurable" according to existing clinical response criteria (RECIST). Therefore, the biomarkers available for assessment of treatment response used by oncologists and radiologists to monitor the response of cancer in the bone needs a quantum advance. Underlying this need is that bone is a common site of residence of metastatic tumors derived from prostate cancer. Imaging using skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging remains essential, with positron emission tomography or single-photon emission computed tomography having potential applicability for diagnosing the presence of bone metastases. However, no consensus exists as to the best modality for diagnosing these lesions or for assessing response to treatment. In this application, we hypothesize that changes in tumor microenvironment (e.g. cell density) will occur early following initiation of successful therapy. Since water within tumor cells is in a restricted environment versus extracellular water, loss of cell membrane integrity has been shown to reduce the diffusion barriers (e.g. restrictions) of water within the tumor, which can be quantified using diffusion MRI. We have recently developed the functional diffusion map (fDM) which is an imaging biomarker analytical approach for quantifying therapeutic-induced changes in the Brownian motion of water within tumor tissue. In this application, we will evaluate the capability of the fDM imaging biomarker for quantification of treatment response in a mouse model of metastatic prostate cancer to the bone. Treatments to be evaluated include ionizing radiation, cytotoxic chemotherapy (docetaxel), anti-angiogenic therapy, molecularly targeted agents and androgen deprivation. Animal studies will provide the data needed to support the use of the fDM imaging biomarker for quantification of the effectiveness of key therapeutic interventions. Clinical studies will also be undertaken to assess the fDM biomarker as an early treatment response marker for outcome assessment in patients treated with androgen deprivation or docetaxel chemotherapy. The ultimate goal of this application is to evaluate the fDM method as a viable, quantifiable imaging biomarker for early monitoring o treatment response in patients with metastatic prostate cancer to the bone. PUBLIC HEALTH RELEVANCE: Overall, this research effort will provide further rationale for initiation of clinical studies with combinations of cytotoxic and molecularly targeted therapies for the treatment of bone cancer. In addition, imaging biomarkers for early assessment of treatment response will be evaluated and validated leading to individualization of treatment for bone cancer patients.

描述（由申请人提供）：随着治疗方法的不断增加，对骨骼中致癌病变的治疗也取得了进展；然而，根据现有的临床反应标准（RECIST），治疗反应被认为是“无法测量的”。因此，肿瘤学家和放射科医生用来评估治疗反应的生物标志物需要取得重大进展，以监测骨中癌症的反应。这一需求的基础是骨是前列腺癌转移性肿瘤的常见驻留部位。使用骨骼闪烁扫描、平片、计算机断层扫描或磁共振成像进行成像仍然是必不可少的，其中正电子发射断层扫描或单光子发射计算机断层扫描对于诊断骨转移的存在具有潜在的适用性。然而，对于诊断这些病变或评估治疗反应的最佳方式尚未达成共识。在此应用中，我们假设肿瘤微环境（例如细胞密度）的变化将在成功治疗开始后早期发生。由于肿瘤细胞内的水与细胞外的水相比处于受限的环境中，细胞膜完整性的丧失已被证明可以减少肿瘤内水的扩散屏障（例如限制），这可以使用扩散 MRI 进行量化。我们最近开发了功能扩散图（fDM），这是一种成像生物标志物分析方法，用于量化治疗引起的肿瘤组织内水的布朗运动的变化。在此应用中，我们将评估 fDM 成像生物标记物在骨转移性前列腺癌小鼠模型中量化治疗反应的能力。待评估的治疗包括电离辐射、细胞毒性化疗（多西紫杉醇）、抗血管生成治疗、分子靶向药物和雄激素剥夺。动物研究将提供支持使用 fDM 成像生物标记物来量化关键治疗干预措施有效性所需的数据。还将进行临床研究来评估 fDM 生物标志物作为早期治疗反应标志物，用于评估接受雄激素剥夺或多西他赛化疗的患者的结果。该应用的最终目标是评估 fDM 方法作为一种可行的、可量化的成像生物标志物，用于早期监测骨转移性前列腺癌患者的治疗反应。公共卫生相关性：总体而言，这项研究工作将为启动细胞毒性和分子靶向疗法相结合治疗骨癌的临床研究提供进一步的理由。此外，将评估和验证用于早期评估治疗反应的成像生物标志物，从而实现骨癌患者的个体化治疗。