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

 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，其基础是单抗(MAb)与近红外(NIR)酞菁染料(IR700)结合，在暴露于近红外光后可导致快速细胞坏死。尽管单次给药(药剂+光)非常有效， 肿瘤内mAb-IR700分布不均匀导致肿瘤复发。随着时间的推移，抗体重新分布到残留的肿瘤中，重复治疗已显示出高度有效的肿瘤治疗。然而，目前监测IR700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-IR700在原位的分布不均一性。因此，个性化的 针对个别受试者量身定制的治疗方案是不可能的。实时监测肿瘤微环境中治疗药物的分布和治疗效果，包括细胞坏死、血流变化和间质变化，将是优化个体化PIT治疗效果的关键。我们假设，多模式针头成像技术可以提供信息，以预测就地(肿瘤内部)凹坑的疗效并实时进行。提出的多模式光学成像技术是基于光学相干层析成像(OCT)和荧光分子成像(FMI)。OCT能够在体内对组织微结构进行高分辨率成像，并已被证明用于肿瘤成像，包括肿瘤边界检测、淋巴管成像和血管成像。FMI提供了高度敏感和特定的治疗剂(MAb-IR700)分布信息，并已被证明可用于监测凹坑效应。我们的实验室开发了一个集成的OCT/FMI成像平台和用于OCT和FMI的小型化针状成像设备。在这项针对NCI Omnibus R03的先导性研究中，我们将探讨多模式成像针技术用于实时监测肿瘤内反应的可行性，以优化PIT的疗效。具体目标是：1)研制多通道OCT/FMI显像针，用于实时监测不同时间点PIT中肿瘤坏死、血流变化及肿瘤细胞活力 2)探讨多模式肿瘤内成像优化PIT治疗效果的可行性。这个项目是一个多学科的合作项目， 在光学成像(UMD博士)和光免疫疗法(Hisataka Kobayashi博士和Peter Choyke博士，NCI)方面具有专业知识的研究人员。由于PIT已成为治疗单抗结合性肿瘤的一种有前途的高选择性和临床可行的治疗方法，且具有最小的非靶点效应，所提出的多通道针状成像技术将为肿瘤微环境的微观监测打开一扇窗，并可能适用于广泛的癌症治疗。

 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.