Monitoring Photo-immunotherapy using Multi-channel Multi-modal Imaging Needles

使用多通道多模式成像针监测光免疫治疗

• 批准号: 8814427
• 负责人: Yu Chen
• 金额: $ 7.6万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8814427
• 关键词: Adverse effects; Angiography; Animal Model; Animals; Antibodies; Antineoplastic Agents; Binding; Blood Vessels; Blood flow; Caliber; Cell Death; Cells; Collaborations; Data; Detection; Diffuse; Dose; Dyes; Effectiveness; Environment; Exposure to; Fluorescence; Frequencies; Hemorrhage; Heterogeneity; Histology; Hour; Image; Imaging Device; Imaging technology; Immunotherapy; In Situ; Individual; Lead; Left; Light; Location; Lymphangiography; Malignant Neoplasms; Measurement; Methods; Molecular; Monitor; Monoclonal Antibodies; Morphology; Necrosis; Needles; Neoplasms in Vascular Tissue; Optical Coherence Tomography; Optics; Performance; Permeability; Pilot Projects; Proliferating; Recurrence; Regimen; Research Personnel; Resolution; Signal Transduction; Speed; Stromal Change; System; Technology; Therapeutic Effect; Time; Tissues; Transportation; Treatment Effectiveness; Treatment Protocols; antibody conjugate; base; cancer cell; cancer therapy; cohort; improved; in vivo; miniaturize; minimally invasive; molecular imaging; mortality; neoplastic cell; optical imaging; phthalocyanine; public health relevance; response; theranostics; tissue phantom; tumor; tumor microenvironment

 DESCRIPTION (provided by applicant): Photo-immunotherapy (PIT) is an emerging low-side-effect cancer therapy based on monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye (IR700) that induces rapid cellular necrosis after exposure to near infrared light. Although single administration of the therapy (agent + light) was highly effective, recurrences were observed due to the inhomogeneous mAb-IR700 distribution in the tumor. Repeated therapy has shown highly effective tumor treatments owing to the redistribution of antibody into the remnant tumor over time. However, current approach for monitoring IR700 fluorescence signal (macroscopic fluorescence reflectance imaging) lacks the resolution and depth selectivity to reveal mAb-IR700 distribution heterogeneity in situ. As a result, personalized treatment regimen tailored to individual subject is not possible. Real-time monitoring of theranostic agent distribution and therapeutic effects including cellular necrosis, blood flow alterations and stromal changes within the tumor micro-environment will be critical for optimizing the effectiveness of individual PIT treatment. We hypothesize that multi-modal needle imaging technology can provide the information to predict the efficacy of PIT in situ (inside the tumor) and in real-time. The proposed multi-modal optical imaging technology is based on optical coherence tomography (OCT) and fluorescence molecular imaging (FMI). OCT enables high-resolution imaging of tissue microstructures in vivo and has been demonstrated for tumor imaging including tumor boundary detection, lymphangiography and angiography. FMI provides highly sensitive and specific information of the theranostic agent (mAB-IR700) distribution and has been demonstrated for monitoring PIT effects. Our lab has developed an integrated OCT/FMI imaging platform and miniaturized needle imaging devices for OCT and FMI. In this pilot study responding to NCI Omnibus R03, we will investigate the feasibility of multi-modal imaging needle technology for real-time monitoring intra-tumor response to optimize the efficacy of PIT. The specific aims are: 1) Develop multi-channel OCT/FMI imaging needle for real-time monitoring of tumor necrosis, blood flow alteration and tumor cell vitality during PIT at different intra-tumor locations; and 2) Investigate the feasibility of multi-modal intra-tumor imaging for optimizing the therapeutic effects of PIT. This project is a multi-disciplinary collaboration among investigators with expertise in optical imaging (Dr. Yu Chen, UMD) and photo-immunotherapy (Drs. Hisataka Kobayashi and Peter Choyke, NCI). As PIT has emerged as a promising highly selective and clinically feasible theranostic method for treatment of mAb-binding tumors with minimal off-target effects, the proposed multi-channel needle imaging technology will open a window for microscopically monitoring of tumor micro-environment, and will likely be applicable to a wide range of cancer therapies.

 描述（由申请人提供）：光免疫疗法（PIT）是一种新兴的低副作用癌症疗法，基于与近红外（NIR）酞菁染料（IR 700）偶联的单克隆抗体（mAb），其在暴露于近红外光后诱导快速细胞坏死。虽然单次给药治疗（药剂+光）是非常有效的， 由于mAb-IR 700在肿瘤中的不均匀分布，观察到复发。由于抗体随着时间的推移重新分布到残余肿瘤中，重复治疗已显示出非常有效的肿瘤治疗方法。然而，目前用于监测IR 700荧光信号的方法（宏观荧光反射成像）缺乏分辨率和深度选择性来揭示mAb-IR 700原位分布异质性。因此，个性化 不可能为个体受试者定制治疗方案。实时监测治疗诊断剂分布和治疗效果，包括肿瘤微环境内的细胞坏死、血流改变和基质变化，对于优化个体PIT治疗的有效性至关重要。我们假设多模式针成像技术可以提供信息来预测原位（肿瘤内部）和实时PIT的疗效。提出的多模态光学成像技术是基于光学相干断层扫描（OCT）和荧光分子成像（FMI）。OCT能够对体内组织微结构进行高分辨率成像，并已被证明可用于肿瘤成像，包括肿瘤边界检测、淋巴管造影和血管造影。FMI提供治疗诊断剂（mAB-IR 700）分布的高度敏感和特异性信息，并已被证明可用于监测PIT效应。我们的实验室已经开发了一个集成的OCT/FMI成像平台和微型针成像设备的OCT和FMI。在这项针对NCI Omnibus R 03的初步研究中，我们将研究多模态成像针技术用于实时监测肿瘤内反应以优化PIT疗效的可行性。具体目标是：1）研制多通道OCT/FMI成像针，用于实时监测不同PIT时肿瘤坏死、血流改变和肿瘤细胞活力。 肿瘤内位置;以及2）研究多模式肿瘤内成像用于优化PIT的治疗效果的可行性。该项目是一个多学科的合作， 具有光学成像（陈宇博士，UMD）和光免疫疗法（Hisataka小林博士和Peter Choyke，NCI）专业知识的研究人员。由于PIT已成为一种有前途的高选择性和临床可行的治疗诊断方法，用于治疗mAb结合肿瘤，具有最小的脱靶效应，因此所提出的多通道针成像技术将为肿瘤微环境的显微镜监测打开一个窗口，并可能适用于广泛的癌症治疗。