Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, United States.
Mol Pharm. 2021 Mar 1;18(3):1238-1246. doi: 10.1021/acs.molpharmaceut.0c01107. Epub 2021 Jan 27.
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses antibody-IRDye700DX (IR700) conjugates and was recently approved in Japan for patients with inoperable head and neck cancer. Exposure of the tumor with NIR light at a wavelength of 690 nm leads to physicochemical changes in the antibody-IR700 conjugate-cell receptor complex, resulting in increased hydrophobicity and damage to the integrity of the cell membrane. However, it is important that the tumor be completely exposed to light during NIR-PIT, and thus, a method to provide real-time information on tumor location would help clinicians direct light more accurately. IR700 is a fluorophore that emits at 702 nm; however, there is no clinically available device optimized for detecting this fluorescence. On the other hand, many indocyanine green (ICG) fluorescence imaging devices have been approved for clinical use in operating rooms. Therefore, we investigated whether LIGHTVISION, one of the clinically available ICG cameras, could be employed for NIR-PIT target tumor detection. Due to the limited benefits of adding IR700 molecules, the additional conjugation of IRDye800CW (IR800) or ICG-EG4-Sulfo-OSu (ICG-EG4), which has an overlapping spectrum with ICG, to trastuzumab-IR700 conjugates was performed. Conjugation of second NIR dyes did not interfere the efficacy of NIR-PIT. The dual conjugation of IR800 and IR700 to trastuzumab clearly visualized target tumors with LIGHTVISION by detecting emission light of IR800. We demonstrated that the conjugation of second NIR dyes enables us to provide a real-time feedback of tumor locations prior to NIR-PIT.
近红外光免疫治疗（NIR-PIT）是一种新开发的癌症治疗方法，使用抗体-IRDye700DX（IR700）缀合物，最近在日本被批准用于无法手术的头颈部癌症患者。用波长为 690nm 的近红外光照射肿瘤会导致抗体-IR700 缀合物-细胞受体复合物的物理化学变化，导致疏水性增加和细胞膜完整性受损。然而，在 NIR-PIT 过程中，肿瘤必须完全暴露在光线下，因此，提供肿瘤位置实时信息的方法将有助于临床医生更准确地引导光线。IR700 是一种荧光团，在 702nm 处发射；然而，目前还没有临床可用的设备来优化检测这种荧光。另一方面，许多吲哚菁绿（ICG）荧光成像设备已被批准在手术室中临床使用。因此，我们研究了临床可用的 ICG 相机之一 LIGHTVISION 是否可用于 NIR-PIT 目标肿瘤检测。由于添加 IR700 分子的益处有限，因此对曲妥珠单抗-IR700 缀合物进行了额外的 IRDye800CW（IR800）或 ICG-EG4-Sulfo-OSu（ICG-EG4）缀合，后者与 ICG 光谱重叠。第二种近红外染料的缀合不干扰 NIR-PIT 的疗效。IR800 和 IR700 双缀合曲妥珠单抗可通过检测 IR800 的发射光，用 LIGHTVISION 清楚地可视化目标肿瘤。我们证明，第二种近红外染料的缀合使我们能够在 NIR-PIT 之前提供肿瘤位置的实时反馈。
