Microfluidic Platform for Preparation of Biomolecule Based Nuclear Imaging Probes

描述（由申请人提供）：该项目的总体目标是开发用于合成癌症生物分子（肽/抗体）靶向核成像探针的微流体技术。目前，这种探针需要由在放射合成方案中有经验的研究级合成化学家合成。这些方法通常需要标记后的HPLC纯化，这增加了额外的时间和对制剂的潜在辐射暴露。开发用于制备用于正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）成像的基于生物分子的成像探针的自动化、可靠且稳健的试剂盒样平台将极大地有益于临床前研究和临床成像两者。拟议项目的重点是开发一种基于微流体的平台，能够制备三种广泛类型的成像探针，包括：（1）靶向生物分子-双官能螯合物缀合物，其然后用所需的放射性金属放射性标记，（2）靶向生物分子，其然后可以与预放射性标记的双官能螯合物缀合，和（3）核心分子，一种或多种靶向肽（或光学成像探针）将与双官能螯合物沿着缀合以络合适当的放射性金属。微流体通过使用小体积的高度浓缩的试剂，广泛使用的放射性金属在水性条件下改进的放射性标记为灵活、高效和自动化的平台提供了基础，用于多种成像剂的合成或常规生产的组合优化，这可以极大地帮助检测肿瘤及其转移。该项目的具体目标是：1。开发用于将各种探针组分共价连接在一起的微流体装置，用所需的放射性金属放射性标记成像探针，并纯化分子探针。2.测试和验证微流体装置和缀合反应，通过使用它们来制备用于癌症成像的放射性标记肽，具有常用的双官能螯合基团和放射性金属。3.在发育良好的荷瘤动物模型中测试和验证放射性标记的肽，以确保探针在体内发挥作用。4.随着单个器件的成功开发，开发一个集成器件，该集成器件包含第一目标的单个器件的优化版本。

DESCRIPTION (provided by applicant): The overall goal of the project is the development of microfluidic technology for the synthesis of biomolecule (peptide/antibody) targeted nuclear imaging probes for cancer. Currently, such probes need to be synthesized by research-level synthetic chemists experienced in radio-synthetic protocols. These methods typically require HPLC purification post-labeling which adds additional time and potential radiation exposure to the preparation. The development of an automated, reliable, and robust kit-like platform for the preparation of biomolecule based imaging probes for either Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging would greatly benefit both, preclinical research and clinical imaging. The proposed project focuses on the development of a microfluidic based platform capable of preparing three broad types of imaging probes consisting of: (1) a targeting biomolecule-bifunctional chelate conjugate which is then radio labeled with a desired radio metal, (2) a targeting biomolecule to which a pre-radio labeled bifunctional chelate can then be conjugated, and (3) a core molecule to which one or more targeting peptides (or optical imaging probes) will be conjugated along with a bifunctional chelate to complex the appropriate radio metal The ability of microfluidics to improve both chemical syntheses by using small volumes of highly concentrated reagents, and improved radio labeling in aqueous conditions with widely utilized radio metals provides the basis for a flexible, efficient, and automated platform for the combinatorial optimization of the syntheses or routine production of an expansive diversity of imaging agents which could greatly aid in the detection of tumors and their metastases. The specific aims of the project are: 1. Develop microfluidic devices for covalently attaching the various probe components together, radio labeling the imaging probe with a desired radio metal, and purifying the molecular probe. 2. Test and validate the microfluidic devices and conjugation reactions by using them to prepare radio labeled peptides used for cancer imaging, with commonly used bifunctional chelate groups and radio metals. 3. Test and validate the radio labeled peptides in a well developed tumor bearing animal model to ensure that the probes function in vivo. 4. With the successful development of the individual devices, develop a single integrated device incorporating the optimized versions of the individual devices of the first aim.