Quantitative Biomarker Imaging for Early Therapy Response Assessment in Cancer

描述（由申请人提供）：迫切需要定量评估癌症治疗反应。CT和标准MRI不能提供关于癌组织的分子、生物化学和生理特性的信息。因此，需要新的定量成像技术和方案来揭示癌症治疗诱导的分子事件的生物标志物。特别是，预测对有效的癌症治疗至关重要的分子靶向途径的早期成像极有可能在未来的患者管理中发挥关键作用。F- 18 FDG-PET可以评估肿瘤对化疗的糖酵解反应，第一个化疗周期后FDG摄取的减少与更好的结果相关。F-18 FLT PET测量细胞增殖率，这是恶性肿瘤的另一个基本过程。细胞凋亡是大多数抗癌药物的主要作用机制，可以通过新型PET示踪剂F-18 ApoSense进行监测。在所有癌症治疗试验中，除灌注MRI外，还将通过DCE MRI测量抗血管生成作用。类似地，MRSI可用于通过测量总胆碱和磷酸胆碱来评估胆碱代谢，其反映膜周转。最后，三重量子过滤钠MRI已被提出来评估肿瘤中的增殖活性和细胞杀伤导致的细胞体积分数的变化。在该项目中，新的定量成像生物标志物的测量将与患者结局和组织生物标志物相结合，以开发用于早期评估癌症治疗反应的预测方法。该项目的总体目标是标准化PET-CT和MRI方案，以准确和可重复地测量癌症治疗试验期间成像生物标志物的变化，以优化后续临床结局的早期预测。将在对分子靶向药物有反应的恶性脑肿瘤中进行定量成像，通过F-18 ApoSense、F-18 FLT和MRI成像。还将在复发性或转移性头颈部鳞状细胞癌中使用针对表皮生长因子受体（EGFR）和血管生成的新型靶向药物（包括血管内皮生长因子（VEGF）和VEGF受体（VEGFR））进行定量成像。成像的类型和时机旨在更具体地测量对药物靶点的影响，以提供治疗反应的最早指标。开发和使用定量成像进行早期治疗评估将大大促进患者管理，使患者免于数周或数月的毒性和无效治疗。相关性（参见说明）：在该项目中，新的定量成像生物标志物的测量将与癌症患者的结果相结合，以开发用于早期评估癌症治疗反应的预测方法。将连续获得并严格定量治疗诱导的肿瘤生物学早期变化的成像生物标志物。开发和使用定量成像进行早期治疗评估将大大促进癌症患者的管理，使患者免于数周或数月的毒性和无效治疗。

DESCRIPTION (provided by applicant): There is a vital need for quantitative assessment of cancer therapy response. CT and standard MRI cannot provide information on the molecular, biochemical and physiologic properties of cancer tissues. Therefore, novel quantitative imaging techniques and protocols are needed to reveal biomarkers of molecular events induced by cancer therapy. In particular, early imaging of molecularly targeted pathways predicted to be essential for effective cancer therapy is highly likely to play a key role in patient management in the future. F- 18 FDG-PET can assess the glycolytic response of tumors to chemotherapy and decreases in FDG uptake after the first chemotherapy cycle correlate with better outcome. F-18 FLT PET measures cell proliferation rate, another fundamental process in malignancy. Apoptosis is the primary mechanism of action of most anticancer drugs and can be monitored by the novel PET tracer F-18 ApoSense. In all cancer therapy trials antiangiogenic effect will be measured by DCE MRI in addition to perfusion MRI. Similarly, MRSI can be used to assess choline metabolism, which reflects membrane turnover, through the measurement of total choline and phosphocholine. Finally, triple quantum filtered sodium MRI has been proposed to assess proliferative activity in tumors and changes in cell volume fraction as a result of cell kill. In this project, measures of novel quantitative imaging biomarkers will be combined with patient outcome and tissue biomarkers to develop predictive methodologies for early assessment of response to cancer therapy. The overarching goal of this project will be to standardize PET-CT and MRI protocols, to accurately and reproducibly measure changes in imaging biomarkers during cancer therapy trials, in order to optimize early predictions of subsequent clinical outcomes. Quantitative imaging will be performed in malignant brain tumors with responses to molecularly targeted agents imaged by F-18 ApoSense, F-18 FLT and MRI. Quantitative imaging will also be performed in recurrent or metastatic squamous cell carcinoma of head and neck using novel targeted agents against epidermal growth factor receptor (EGFR) and angiogenesis, including vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR). The type and timing of imaging are aimed at more specific measurements of the effects on the drug target, to provide the earliest indicator of therapeutic response. Development and use of quantitative imaging for early therapy assessment will greatly facilitate patient management, by sparing patients from weeks or months of toxicity and ineffective treatment. RELEVANCE (See instructions): In this project, measures of novel quantitative imaging biomarkers will be combined with cancer patient outcome to develop predictive methodologies for early assessment of response to cancer therapy. Imaging biomarkers of therapy induced early changes in tumor biology will be serially obtained and rigidly quantified. Development and use of quantitative imaging for early therapy assessment will greatly facilitate cancer patient management by sparing patients from weeks or months of toxicity and ineffective treatment.