Fluorescence Imaging of Tumor-Accumulating Antibody-IR700 Conjugates Prior to Near-Infrared Photoimmunotherapy (NIR-PIT) Using a Commercially Available Camera Designed for Indocyanine Green.

Fluorescence Imaging of Tumor-Accumulating Antibody-IR700 Conjugates Prior to Near-Infrared Photoimmunotherapy (NIR-PIT) Using a Commercially Available Camera Designed for Indocyanine Green.
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近红外光免疫治疗(NIR-PIT)前肿瘤蓄积抗体-IR 700偶联物的荧光成像,使用为吲哚菁绿色设计的市售照相机。

DOI:
10.1021/acs.molpharmaceut.0c01107
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发表时间:
2021-03-01
影响因子:
4.9
通讯作者:
Kobayashi, Hisataka
Kobayashi, Hisataka
中科院分区:
医学2区
文献类型:
--
作者:
Inagaki, Fuyuki F.;Fujimura, Daiki;Furusawa, Aki;Okada, Ryuhei;Wakiyama, Hiroaki;Kato, Takuya;Choyke, Peter L.;Kobayashi, Hisataka

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近红外光免疫疗法(NIR-PIT)是一种新开发的癌症治疗方法,使用抗体-IRDye 700DX(IR 700)缀合物,最近在日本被批准用于不可手术的头颈癌患者。肿瘤暴露于波长为690 nm的NIR光导致抗体-IR 700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,重要的是肿瘤在NIR-PIT期间完全暴露于光,因此,提供关于肿瘤位置的实时信息的方法将帮助临床医生更准确地引导光。IR 700是一种在702 nm处发射的荧光团;然而,目前还没有临床上可用于检测这种荧光的优化设备。另一方面,许多吲哚菁绿色(ICG)荧光成像装置已被批准用于手术室中的临床使用。因此,我们研究了临床可用的ICG相机之一LIGHTVISION是否可以用于NIR-PIT靶肿瘤检测。由于添加IR 700分子的益处有限,因此进行了IRDye 800 CW(IR 800)或ICG-EG 4-Sulfo-OSu(ICG-EG 4)(其与ICG具有重叠光谱)与曲妥珠单抗-IR 700缀合物的额外缀合。第二NIR染料的缀合不干扰NIR-PIT的功效。IR 800和IR 700与曲妥珠单抗的双重缀合通过检测IR 800的发射光用LIGHTVISION清楚地可视化靶肿瘤。我们证明了第二NIR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。
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.
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