In vivo Macroscopic Fluorescence Lifetime Molecular Optical Imaging

活体时间分辨广场分子光学断层扫描(亲本R01) 摘要 在体内，特别是在临床之前，仍需要更好地确定新的靶向治疗的特征。 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。 输油管道。然而，仍然缺乏能够实现纵向(多次)的集成成像平台 点)和空间分辨率监测复杂指纹，包括分子、代谢和功能 同一肿瘤/受试者的签名。这一新的集成多路传输成像平台将发挥关键作用 在开发下一代靶向药物和阐明(多重)耐药机制方面。 最近，我们展示了光学成像在量化受体靶标方面的独特能力。 通过利用荧光寿命参与活体受试者。这一突出成就是实现的 由于仪器、算法和生物化学创新的结合，第一次能够， 基于二维或三维Förster共振能量结构光的全身时间分辨光学成像 活体受试者的转移(FRET)成像。在此，使用RFA-CA-20-021版本申请 纳入NCI支持的技术以加速癌症研究，我们建议扩大 亲本R01，并利用IMAT资助的表位抗体技术对体内和非 宏观荧光寿命评价HER2受体靶向给药系统的侵袭性 成像(Mfli)-FRET成像。我们将建立和优化抗体-靶向成像管道，以 定量监测近红外标记的抗HER2表位抗体与其各自的结合 异质乳腺肿瘤微环境中的靶点(靶点交战)。

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.