SBIR Phase I: Bioluminescence Resonance Energy Transfer Probes for Molecular Imaging

这项小型企业创新研究（SBIR）第一阶段项目将展示利用新的靶向生物发光共振能量转移到量子点（BRET-QD）技术检测癌症诊断和治疗中的既定目标。与荧光或发光成像相比，BRET-QD提供了实质性的优势：(1)在提供相当或更好的灵敏度的同时，避免了对外部照明的需要；(2)，提供与现有图像捕获技术的兼容性；(3)与放射性标签技术相比，提供更好的探针稳定性，使纵向研究成为可能；(4)比基于荧光的探针提供更大的体内穿透深度。该项目将演示在乳腺癌细胞系中直接检测HER2癌症标志物。在乳腺癌细胞系的活细胞中成功检测HER2将为推进BRET-QD探针在小动物中的直接肿瘤和组织成像提供必要的概念证明。本研究更广泛的影响是开发了一种灵敏、便捷的靶向成像探针平台，并将其应用于乳腺癌检测。为了了解诸如癌症等疾病的分子机制，人们对从基于细胞的检测发展到在小动物模型中进行疾病状态的体内成像越来越感兴趣。靶向BRET-QD平台将为荧光和生物发光成像探针技术提供一种经济、方便、有效的替代方案。除了癌症应用，该平台将适用于几乎任何需要通过生物素化抗体或其他生物素化分子对已知分子进行敏感检测的研究。

This Small Business Innovation Research (SBIR) Phase I project will demonstrate the detection of an established target in cancer diagnosis and treatment using new targeted Bioluminescence Resonance Energy Transfer to Quantum Dots (BRET-QD) technology. BRET-QD offers substantial advantages over fluorescence or luminescence imaging by: (1), circumventing the need for external illumination while delivering comparable or better sensitivity; (2), providing compatibility with existing image capturing technology; (3), providing superior probe stability compared to radiolabel technology, enabling longitudinal studies; and (4), delivering greater in vivo penetration-depth than fluorescence-based probes. The project will demonstrate the direct detection of the HER2 cancer marker in breast cancer cell lines. Successful detection of HER2 in live cells from a breast cancer cell line will provide the proof-of-concept necessary for advancing to direct tumor and tissue imaging with BRET-QD probes in small animals.The broader impacts of this research are the development of a sensitive and convenient targeted imaging probe platform and its application to breast cancer detection. In order to understand the molecular mechanisms underlying diseases such as cancer, there is increasing interest in advancing from cell-based assays to in vivo imaging of disease states in small animal models. The targeted BRET-QD platform will provide a cost-effective, convenient and effective alternative to fluorescence and bioluminescence imaging probe technology. In addition to cancer applications, this platform will be applicable to virtually any investigation requiring sensitive detection of a known molecule that can be targeted via a biotinylated antibody or other biotinylated molecule.