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 当前基于成像的技术用于定量评估组织灌注需要复杂的数据 获取和分析策略；通常需要辅助血液采样以测量输入 功能；仅限于单个器官或组织区域；而且由于它们的复杂性并不适合作为一个 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） bis（硫代氨基芳基）复合物，Cu-et和Cu-etm将提供一个定量估计的平台 整个全身图像的组织灌注，利用快速和计算的方法 适用于广泛的常规临床应用。这个学术工业伙伴关系的目的 建议是将非常有希望的初始结果转化为经过全面验证的全身定量灌注 在癌症临床试验和精密医学治疗策略中用作生物标志物的成像方法。 这种合作伙伴关系将汇集三个关键调查人员团队：i。充分发展和验证62CU 定量灌注法（印第安纳大学）； ii。优化62ZN/62CU发电机生产技术 启用广泛发电机分布（Zevacor Molecular，Inc。）；和iii。建立软件处理 促进跨不同成像中心（MIM Software，Inc。和Inc.和 印第安纳大学）。这项研究的重要性包括：（1）定量评估 治疗剂对整个体内肿瘤的血管作用； （2）评估非目标副作用 整个身体的组织； （3）在原发性和转移性病变中建立疾病表型 （和患者预后）通过结合全身代谢和灌注测量； （4）监视 肿瘤从药物反应到耐药表型的过渡（和/或评估的耐用性 回复）; （5）评估表现出灌注异常的合并症的程度（例如， 心血管，脑血管，肾脏和周围血管疾病，糖尿病，甲状腺功能）； （6）广泛 分发62ZN/62CU发电机以满足临床试验和患者护理需求； （7）和谐 通过标准化的定量数据在不同的成像环境中实施此方法 图像分析工具。这项研究的关键创新将是定量全身的进步 研究实验室的灌注成像方法，成为一组完整的经过验证的工具，可实现强大 以及整个成像界的临床试验和患者护理中的标准化应用。