Integrated Tools for Quantitative Whole-Body Tumor Perfusion Imaging

摘要 目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以测量输入 功能;限于单个器官或组织区域;并且由于其复杂性，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62 Cu标记的铜（II） 双（缩氨基硫脲）配合物，Cu-ETS和Cu-ETSM，将提供一个平台，定量评估 整个全身图像的组织灌注，利用快速和计算的方法， 适用于广泛常规临床应用。这种学术-工业伙伴关系的目标是 一项建议是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确医学治疗策略中用作生物标志物的成像方法。 这一伙伴关系将汇集三个主要的调查小组，以便：全面开发和验证62 Cu 定量灌注方法（印第安纳州大学）; ii.完善62 Zn/62 Cu发电机生产工艺， 实现广泛的发生器分布（Zevacor Molecular，Inc.）;和三.建立一个软件处理 平台，以促进跨不同成像中心的数据分析的协调（MIM Software，Inc.和 印第安纳州大学）。本研究的意义在于：（1）定量评估 治疗剂对全身肿瘤的血管作用;（2）评估治疗中的非靶向副作用。 （3）在原发性和转移性病变中建立疾病表型 (and患者预后）通过结合全身代谢和灌注测量;（4）监测 肿瘤从药物应答表型向耐药表型的转变（和/或评估 响应）;（5）评估表现为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62 Zn/62 Cu发生器，以满足临床试验和患者护理需求;（7）协调 通过标准化的定量数据在不同的成像环境中实现该方法， 图像分析工具。本研究的主要创新之处在于提出了一种定量的全身 将研究实验室的灌注成像方法转化为一套完整的经验证的工具， 以及在整个成像领域的临床试验和患者护理中的标准化应用。

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.