Integrated Tools for Quantitative Whole-Body Tumor Perfusion Imaging

用于定量全身肿瘤灌注成像的集成工具

• 批准号: 9975758
• 负责人: MARK A GREEN
• 金额: $ 57.28万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9975758
• 关键词: Age; Anatomy; Animal Model; Biological; Biological Markers; Blood Vessels; Blood specimen; Cardiovascular system; Characteristics; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Communities; Complex; Computer software; Copper; Cyclic GMP; Data Analyses; Databases; Development; Diabetes Mellitus; Diagnostic; Disease; Drug Kinetics; Drug resistance; Environment; Evaluation; Evolution; Family suidae; Generations; Head and Neck Cancer; Head and neck structure; Human; Image; Image Analysis; Indiana; Investigation; Kidney; Knowledge; Label; Laboratory Research; Lead; Malignant Neoplasms; Measurement; Metabolism; Methodology; Methods; Microspheres; Molecular; Monitor; Multi-Institutional Clinical Trial; Neoplasm Metastasis; Normal tissue morphology; Nutrient; Organ; Oxygen; Patient Care; Patients; Perfusion; Peripheral Vascular Diseases; Pharmaceutical Preparations; Phenotype; Physiology; Play; Primary Lesion; Process; Production; Property; Radiolabeled; Reference Standards; Renal Cell Carcinoma; Reproducibility; Research; Research Methodology; Research Personnel; Role; Site; Standardization; System; Technical Expertise; Techniques; Technology; Testing; Therapeutic Agents; Therapeutic Effect; Thiosemicarbazones; Thyroid Function Tests; Tissues; Tracer; Translating; Treatment Protocols; Universities; Validation; Vascular System; Vendor; angiogenesis; base; cancer biomarkers; cancer clinical trial; cancer therapy; cerebrovascular; clinical application; clinical center; clinical implementation; clinical investigation; clinical practice; clinically relevant; comorbidity; complex data; data acquisition; data harmonization; design; disease phenotype; experience; human subject; image processing; imaging modality; individualized medicine; industry partner; innovation; kinetic model; melanoma; novel; novel anticancer drug; outcome forecast; perfusion imaging; precision medicine; prototype; rapid technique; response; side effect; technology validation; tool; treatment strategy; treatment trial; tumor; tumor progression; whole body imaging

Abstract Current imaging-based techniques for quantitative assessment of tissue perfusion require complex data acquisition and analysis strategies; typically require ancillary blood sampling for measurement of input functions; are limited to a single organ or tissue region; and because of their complexity are not well suited as a biomarker for cancer clinical trials or patient management. We hypothesize that the 62Cu-labeled copper(II) bis(thiosemicarbazone) complexes, Cu-ETS and Cu-ETSM, will provide a platform for quantitative estimation of tissue perfusion throughout whole-body images utilizing methods that are rapid, and computationally suitable, for widespread routine clinical application. The objective of this academic-industrial partnership proposal is to translate very promising initial results into a fully validated whole-body quantitative perfusion imaging method for use as a biomarker in cancer clinical trials and precision medicine treatment strategies. This partnership will bring together three key teams of investigators to: i. fully develop and validate the 62Cu quantitative perfusion method (Indiana University); ii. refine the 62Zn/62Cu generator production technology to enable wide-spread generator distribution (Zevacor Molecular, Inc.); and iii. to establish a software processing platform to facilitate harmonization of data analysis across diverse imaging centers (MIM Software, Inc. and Indiana University). The significance of this research includes the abilities to: (1) quantitatively assess the vascular effects of therapeutic agents on tumors throughout the body; (2) assess non-target side-effects in tissues throughout the whole body; (3) establish disease phenotype in both primary and metastatic lesions (and patient prognosis) by combining whole-body metabolism and perfusion measurements; (4) monitor the transition of tumors from a drug-responsive to a drug-resistant phenotype (and/or assess durability of response); (5) assess the extent of comorbidities that manifest with perfusion abnormalities (e.g., cardiovascular, cerebrovascular, renal, and peripheral vascular diseases, diabetes, thyroid function); (6) widely distribute 62Zn/62Cu generators to meet clinical trial and patient care demands; and (7) harmonize implementation of this method across diverse imaging environments via standardized quantitative data and image analysis tools. The key innovation of this research will be advancement of a quantitative whole-body perfusion imaging method from the research laboratory into a complete set of validated tools that enable robust and standardized application in clinical trials and patient care throughout the imaging community.

抽象的 当前用于定量评估组织灌注的基于成像的技术需要复杂的数据 采集和分析策略；通常需要辅助血液采样来测量输入 功能；仅限于单个器官或组织区域；并且由于它们的复杂性不太适合作为 用于癌症临床试验或患者管理的生物标志物。我们假设 62Cu 标记的铜(II) 双（缩氨基硫脲）配合物 Cu-ETS 和 Cu-ETSM 将为定量评估提供平台 利用快速且可计算的方法在整个身体图像中进行组织灌注 适合广泛的常规临床应用。这种学术与工业合作伙伴关系的目标 建议是将非常有希望的初步结果转化为经过充分验证的全身定量灌注 成像方法用作癌症临床试验和精准医学治疗策略中的生物标志物。 此次合作将汇集三个关键的研究团队，以：全面开发和验证62Cu 定量灌注法（印第安纳大学）；二.完善62Zn/62Cu发电机生产技术 实现发电机的广泛分布（Zevacor Molecular, Inc.）；和 iii.建立软件处理 平台，以促进不同成像中心之间数据分析的协调（MIM Software, Inc. 和 印第安纳大学）。这项研究的意义包括能够：（1）定量评估 治疗药物对全身肿瘤的血管作用； (2) 评估非目标副作用 遍布全身的组织； (3) 建立原发性和转移性病变的疾病表型 （和患者预后）结合全身代谢和灌注测量； (4) 监控 肿瘤从药物反应性到耐药性表型的转变（和/或评估药物的持久性） 回复）; (5) 评估以灌注异常表现的合并症的程度（例如， 心脑血管、肾及周围血管疾病、糖尿病、甲状腺功能）； (6)广泛 分销62Zn/62Cu发电机以满足临床试验和患者护理需求； (7) 协调 通过标准化定量数据在不同的成像环境中实施该方法 图像分析工具。这项研究的关键创新点是定量全身的进步 灌注成像方法从研究实验室转变为一整套经过验证的工具，可实现稳健的 以及整个影像界临床试验和患者护理中的标准化应用。