Novel Monomolecular Multi Modality Imaging Agents

描述(由申请人提供)： 分子成像时代需要发展分子探针，以探询发病的分子基础。不幸的是，体内异常的分子过程通常涉及少量靶向因子的表达，而这些靶向因子只能通过高度敏感的诊断方法来检测。因此，核成像方法适合于分子成像，因为它可以在组织中检测到最少量的放射性药物。最近的研究表明，通过使用多模式成像系统从每种成分成像方法中提供补充和独特的诊断信息，可以实现对癌细胞的准确和快速检测。通过多模式成像方法进行体内肿瘤的分子成像将受益于单分子多模式显像剂(MOMIAS)的发展。因此，本研究致力于开发用于肿瘤成像的新型光核MOMIA。建议分子的结构框架将包括用于增强肿瘤特异性的受体特异性载体，用于光学成像的近红外荧光染料，以及用于伽马闪烁成像(111In)、正电子发射断层扫描(64Cu)或伽马闪烁和放射治疗相结合的螯合放射性金属(177Lu)。将对新的MOMIAS进行稳定性、细胞毒性和亚细胞分布的测试，以选择有希望的候选者进行体内评估。体内研究将包括选定的莫米亚的药代动力学和组织学。啮齿动物肿瘤的定位将通过荧光、伽马和正电子发射成像进行，并将来自所有模式的数据相互比较。这项研究的成功完成将导致至少一种MOMIA的开发，用于翻译研究和最终的临床应用。

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.