In vivo Macroscopic Fluorescence Lifetime Molecular Optical Imaging

体内宏观荧光寿命分子光学成像

• 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
• 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

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.

体内时间分辨宽场分子光学断层扫描（母体R 01） 摘要 仍然非常需要在体内更好地表征新的靶向疗法，特别是在临床应用之前。 翻译.在这方面，临床前分子成像是靶向药物开发的核心工具 渠道.然而，仍然缺乏能够实现纵向（多次）成像的集成成像平台。 点）和空间分辨的复杂指纹监测，包括分子，代谢和功能 在同一肿瘤/受试者中的签名。这一新的综合多路成像平台将发挥至关重要的作用 在开发下一代靶向药物和阐明（多）耐药机制方面。 最近，我们已经证明了光学成像在定量受体靶点方面的独特能力。 通过利用荧光寿命参与活体受试者。这一优异成绩实现了 由于仪器、算法和生物化学创新的结合，第一次， 基于结构光的全身时间分辨光学成像，用于2D或3D Förster共振能量 转移（FRET）成像。在此，使用RFA-CA-20-021， 结合NCI支持的技术，以加速癌症研究，我们建议扩大 亲本R 01，并采用IMAT资助的中间位抗体技术来定量监测体内和非 使用宏观荧光寿命的HER 2受体靶向药物递送系统的侵入性功效 成像（MFLI）-FRET成像。我们将建立和优化抗体到靶点成像管道， 定量监测近红外标记的抗HER 2中间位抗体与它们各自的 靶点（靶点接合）在异质性乳腺肿瘤微环境中的作用。