In vivo Macroscopic Fluorescence Lifetime Molecular Optical Imaging

体内宏观荧光寿命分子光学成像

基本信息

批准号：
10277118
负责人：
Margarida Barroso
金额：
$ 19.04万
依托单位：
RENSSELAER POLYTECHNIC INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10277118
关键词：
3-Dimensional Achievement Algorithms Animals Antibodies Aspartate Binding Biochemical Biological Assay Blood Cancer Biology Cell Surface Proteins Cities Cleaved cell Complex Coupled Development Drug Delivery Systems Drug Receptors Drug Targeting Dyes ERBB2 gene Epidermal Growth Factor Receptor Fingerprint Fluorescence Fluorescence Microscopy Fluorescence Resonance Energy Transfer Functional Imaging Funding Goals Human Image Image-Guided Surgery In Vitro Label Length Libraries Light MMP9 gene Mammary Neoplasms Masks Measures Metabolic Microscopy Molecular Monitor Monoclonal Antibodies Multi-Drug Resistance Oncology Optical Tomography Parents Peptide Hydrolases Pharmaceutical Preparations Pharmacologic Substance Play Positioning Attribute Property Reporting Research Role Series Side Signal Transduction Site Structure Technology Testing Therapeutic Therapeutic Monoclonal Antibodies Time Tissues Toxic effect Toxin Trastuzumab antibody engineering anticancer research base cancer imaging clinical translation clinically relevant deep learning detection sensitivity drug development fluorescence lifetime imaging imager imaging modality imaging platform imaging study improved in vivo in vivo Model in vivo imaging in vivo monitoring innovation interstitial macromolecule malignant breast neoplasm metabolic imaging molecular imaging multiplexed imaging new technology new therapeutic target next generation novel optical imaging personalized medicine pre-clinical preclinical imaging programs quantitative imaging receptor receptor binding resistance mechanism response serial imaging success targeted delivery targeted imaging targeted treatment technological innovation tool trafficking tumor tumor microenvironment tumor xenograft

项目摘要

In vivo Time-Resolved Wide-Field Molecular Optical Tomography (Parent R01) ABSTRACT There is still great need in better characterizing new targeted therapies in vivo, especially prior to clinical translation. In this regard, preclinical molecular imaging is a central tool in the targeted drug development pipeline. However, there is still a lack of integrated imaging platforms that can enable longitudinal (multiple time points) and spatially-resolved monitoring of complex fingerprints including molecular, metabolic and functional signatures in the same tumor/subject. This new integrated multiplexing imaging platform will play a crucial role in the development of the next generation of targeted drugs and elucidating (multi-) drug resistance mechanisms. Recently, we have demonstrated the unique capabilities of optical imaging in quantifying receptor-target engagement in live subjects by leveraging fluorescence lifetime. This outstanding achievement was realized thanks to the combination of instrumental, algorithmic and biochemical innovations to enable, for the first time, whole-body time-resolved optical imaging based on structured light for 2D or 3D Förster resonance energy transfer (FRET) imaging in live subjects. Herein, using the RFA-CA-20-021, Revision Applications for Incorporation of NCI-Supported Technology to Accelerate Cancer Research, we propose to expand on the parent R01 and employ the IMAT-funded meditope antibody technology to quantitatively monitor in vivo and non- invasively the efficacy of HER2 receptor-targeted drug delivery systems using macroscopy fluorescence lifetime imaging (MFLI)-FRET imaging. We will establish and optimize an antibody-to-target imaging pipeline to quantitatively monitor the binding of near-infrared labeled anti-HER2 meditope antibodies to their respective targets (target engagement) in heterogeneous breast tumor microenvironments.

体内时间分辨的宽场分子光学断层扫描（父R01）抽象的仍然需要更好地表征体内新的靶向疗法，尤其是在临床之前翻译。在这方面，临床前分子成像是靶向药物开发的中心工具管道。但是，仍然缺乏可以实现纵向的集成成像平台（多次点）和对复杂指纹的空间分辨监测，包括分子，代谢和功能同一肿瘤/受试者的签名。这个新的集成多路复用成像平台将发挥关键作用在下一代有靶向药物和阐明（多）耐药性机制的发展中。最近，我们证明了光学成像在量化接收器目标方面的独特功能通过利用荧光寿命来参与实时受试者。实现了这一出色的成就感谢乐器，算法和生化创新的结合，这是首次启用基于2D或3Dförster共振能的结构光的全身时间分辨光学成像在现场主题中转移（FRET）成像。此处使用RFA-CA-20-021，修订应用程序将NCI支持的技术纳入加速癌症研究，我们建议扩展父级R01并采用IMAT资助的媒体抗体技术来定量监测体内和非 - 使用宏观荧光寿命，侵入式HER2受体靶向药物输送系统的效率成像（MFLI）-Fret成像。我们将建立并优化抗体至目标成像管道定量监测近红外标记的抗HER2 MUDITOPE抗体与它们的结合异质乳腺肿瘤微环境中的靶标（目标参与）。