Integrated Tools for Quantitative Whole-Body Tumor Perfusion Imaging

摘要 目前基于成像的组织血流灌注定量评估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；限于单个器官或组织区域；由于它们的复杂性，不太适合作为 癌症临床试验或患者管理的生物标记物。我们推测62Cu标记的铜(II) 缩氨基硫脲(BIS)配合物，即铜-ETS和铜-ETSM，将为定量评估提供平台 利用快速和计算的方法，在全身图像中进行组织灌流 适用于临床广泛的常规应用。这种学术和产业伙伴关系的目标是 建议将非常有希望的初步结果转化为完全有效的全身定量灌注 在癌症临床试验和精准医学治疗策略中用作生物标志物的成像方法。 这一伙伴关系将把三个关键的调查团队聚集在一起：I.全面开发和验证62Cu2 定量灌注法(印第安纳大学)；精炼62Zn/62Cu发电机生产技术 实现广泛的发电机分布(Zevacal或分子公司)；以及要建立一套软件流程 促进跨不同成像中心(MIM Software，Inc.和 印第安纳大学)。本研究的意义包括：(1)定量评估 治疗药物对全身肿瘤的血管效应；(2)评估非靶向副作用 全身的组织；(3)在原发灶和转移灶中建立疾病表型 (和患者预后)；(4)监测 肿瘤从药物反应到耐药表型的转变(和/或评估 响应)；(5)评估表现为灌注异常的共病的程度(例如， 心血管、脑血管、肾脏和外周血管疾病、糖尿病、甲状腺功能)；(6)广泛 分发62锌/62铜发电机，以满足临床试验和患者护理需求；以及(7)协调 在不同的成像环境中通过标准化的定量数据和 图像分析工具。这项研究的关键创新之处将是全面量化的发展。 将灌注成像方法从研究实验室转化为一整套经过验证的工具，从而实现健壮 并在整个成像社区的临床试验和患者护理中进行标准化应用。

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.