Microfluidic Platform for Preparation of Biomolecule Based Nuclear Imaging Probes

项目描述（由申请人提供）：该项目的总体目标是开发用于合成生物分子（肽/抗体）靶向癌症核成像探针的微流控技术。目前，这种探针需要由在放射性合成方案方面经验丰富的研究级合成化学家合成。这些方法通常需要HPLC纯化后标记，这增加了额外的时间和潜在的辐射暴露于制备。开发一种自动化的、可靠的、健壮的试剂盒式平台，用于制备基于生物分子的成像探针，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，将极大地有利于临床前研究和临床成像。拟议的项目侧重于开发一种基于微流体的平台，该平台能够制备三种类型的成像探针，包括：(1)靶向生物分子-双功能螯合物偶联物，然后用所需的无线电金属对其进行无线电标记；(2)靶向生物分子，然后将预先无线电标记的双功能螯合物偶联到其上；(3)将一个或多个靶向肽（或光学成像探针）与双功能螯合物结合的核心分子，以使适当的放射性金属复合。微流体通过使用小体积高浓度试剂改善化学合成的能力，以及在广泛使用的放射性金属的水条件下改进放射性标记的能力，为灵活，高效，以及用于合成或常规生产多种显像剂的组合优化的自动化平台，这些显像剂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。开发微流体装置，将各种探针组件共价连接在一起，用所需的放射性金属对成像探针进行放射性标记，并纯化分子探针。2. 测试和验证微流控装置和偶联反应，使用它们制备用于癌症成像的放射性标记肽，常用的双功能螯合基团和放射性金属。3. 在成熟的荷瘤动物模型中测试和验证放射性标记肽，以确保探针在体内发挥作用。4. 随着单个器件的成功开发，开发包含第一个目标的单个器件的优化版本的单个集成器件。

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.