Quantitative Biomarker Imaging for Early Therapy Response Assessment in Cancer

描述(由申请人提供)：对癌症治疗反应进行量化评估是非常必要的。CT和标准MRI不能提供有关癌症组织的分子、生化和生理特性的信息。因此，需要新的定量成像技术和方案来揭示由癌症治疗引起的分子事件的生物标记物。特别是，预测对有效的癌症治疗至关重要的分子靶向通路的早期成像很可能在未来的患者管理中发挥关键作用。F-18FDG-PET可以评估肿瘤对化疗的糖酵解反应，在第一个化疗周期后FDG摄取减少与较好的结果相关。F-18Flt 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，还将用DCE MRI测量抗血管生成的效果。同样，MRSI可以通过测量总胆碱和磷胆碱来评估胆碱代谢，它反映了膜的周转。最后，三量子滤波钠磁共振成像被建议用于评估肿瘤的增殖活性和细胞杀伤导致的细胞体积分数的变化。在这个项目中，新的定量成像生物标记物的测量将与患者预后和组织生物标记物相结合，以开发早期评估癌症治疗反应的预测方法。该项目的总体目标将是标准化PET-CT和MRI方案，准确和可重复性地测量癌症治疗试验期间成像生物标记物的变化，以便优化对后续临床结果的早期预测。对F-18 ApoSense、F-18 Flt和MRI成像的分子靶向药物的反应将在恶性脑肿瘤中进行定量成像。还将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)和血管内皮生长因子受体(VEGFR)，对复发或转移性头颈部鳞状细胞癌进行定量成像。成像的类型和时间旨在对药物靶标的影响进行更具体的测量，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极大地方便患者的管理，使患者免于数周或数月的毒性和无效治疗。相关性(见说明)：在这个项目中，新的定量成像生物标记物的测量将与癌症患者的结果相结合，以开发预测方法，用于癌症治疗反应的早期评估。治疗引起的肿瘤生物学早期变化的成像生物标志物将被连续获得并严格量化。开发和使用用于早期治疗评估的定量成像技术将极大地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.