Novel Monomolecular Multi Modality Imaging Agents

描述（由申请人提供）： 分子影像学时代的到来，要求开发能够探究发病机制的分子基础的分子探针。不幸的是，体内异常分子过程通常涉及少量靶因子的表达，这些靶因子只能通过高度灵敏的诊断方法检测到。出于这个原因，核成像方法，可以检测组织中的放射性药物的最小量，适合于分子成像。最近的研究表明，可以通过使用多模态成像系统来实现癌细胞的准确和快速检测，以提供来自每个组件成像方法的互补和独特的诊断信息。通过多模态成像方法进行体内癌症的分子成像将受益于单分子多模态成像剂（MOMIA）的发展。因此，本研究的重点是开发新的光学核MOMIA成像肿瘤。所提出的分子的结构框架将由增强肿瘤特异性的受体特异性载体、用于光学成像的NIR荧光染料以及用于伽马射线照相术（111In）、正电子发射断层扫描术（64Cu）或联合伽马射线照相术和放射疗法（177Lu）的螯合放射性金属组成。将进行新MOMIA的稳定性、细胞毒性和亚细胞分布，以选择有希望的候选物进行体内评价。体内研究将包括选定MOMIA的药代动力学和组织学。将通过荧光、伽马射线和正电子发射成像对啮齿动物中的肿瘤进行定位，并将来自所有模态的数据相互比较。本研究的成功完成将导致至少开发一种MOMIA用于转化研究和最终临床使用。

DESCRIPTION (provided by applicant): The era of molecular imaging necessitates the development of molecular probes that can interrogate the molecular basis of pathogenesis. Unfortunately, aberrant molecular processes in vivo typically involve the expression of small amounts of target factors that can only be detected by highly sensitive diagnostic methods. For this reason, nuclear imaging methods, which can detect minimal amounts of radiopharmaceuticals in tissues, are suited for molecular imaging. Recent studies have shown that accurate and rapid detection of cancer cells can be achieved by the use of multimodal imaging systems to furnish complementary and unique diagnostic information from each component imaging method. Molecular imaging of cancer in vivo by multimodality imaging methods would benefit from the development of monomolecular multimodality imaging agents (MOMIAs). Accordingly, this study focuses on the development of novel optical-nuclear MOMIAs for imaging tumors. The structural framework of the proposed molecules will consist of a receptor-specific carrier to enhance tumor specificity, a NIR fluorescent dye for optical imaging, and a chelated radiometal for gamma scintigraphy (111In), positron emission tomography (64Cu) or combined gamma scintigraphy and radiotherapy (177Lu). Stability, cytotoxicity and subcellular distribution of the new MOMIAs will be performed to select promising candidates for in vivo evaluation. The in vivo studies will include pharmacokinetics and histology of selected MOMIAs. Localization of tumors in rodents will be performed by fluorescence, gamma, and positron emission imaging, and the data from all modalities will be compared with each other. Successful completion of this study will result in the development of at least one MOMIA for translational research and eventual clinical use.