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Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy.
Contrast Media & Molecular Imaging Pub Date : 2014-04-08 , DOI: 10.1002/cmmi.1570
Towhid Ali 1 , Takahito Nakajima , Kohei Sano , Kazuhide Sato , Peter L Choyke , Hisataka Kobayashi
Affiliation  

A new type of monoclonal antibody (mAb)-based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a near-infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, target-selective necrotic cell death. However, tumor shrinkage takes several days to occur, making it difficult to detect earlier changes in the tumor. In this study, Panitumumab targeting the epidermal growth factor receptor (EGFR1) conjugated to IR700 was used to treat EGFR-expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100 J cm(-2)) in xenograft tumors in mice. Indocyanine green (ICG) dynamic imaging was evaluated for monitoring cytotoxic effects for the first hour after PIT. Our results demonstrated a statistical difference (p < 0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50 J cm(-2): 2.94 ± 0.35 vs 5.22 ± 0.92, p = 0.02; and 100 J cm(-2) : 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) as early as 20 min post ICG injection. However, no significant difference (p > 0.05) in ICG intensity between control and PIT treated tumors was evident in the lower light exposure group at any time points up to 60 min (10 J cm(-2) : 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; and 30 J cm(-2): 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07). Similarly, the retention index (background to corrected uptake ratio of ICG) varied with light exposure. In conclusion, ICG may serve as a potential indicator of acute cytotoxic effects of mAb-IR700-induced PIT even before morphological changes can be seen in targeted tumors.

中文翻译:

用吲哚菁绿动态荧光成像监测光免疫疗法的治疗效果。

最近描述了一种基于单克隆抗体 (mAb) 的新型高特异性光疗(光免疫疗法;PIT),它使用与 mAb 偶联的近红外 (NIR) 酞菁染料 IRDye700DX (IR700)。近红外光照射会导致立即的、目标选择性的坏死细胞死亡。然而,肿瘤缩小需要几天的时间,因此很难检测到肿瘤的早期变化。在这项研究中,靶向与 IR700 偶联的表皮生长因子受体 (EGFR1) 的帕尼单抗用于治疗表达 EGFR 的 A431 肿瘤细胞和体内异种移植物。PIT 是在不同剂量的近红外光 (10、30、50 和 100 J cm(-2)) 中进行的,在小鼠的异种移植肿瘤中。吲哚菁绿 (ICG) 动态成像用于监测 PIT 后第一小时的细胞毒性作用。我们的结果表明,在较高光照组(50 J cm(-2):2.94 ± 0.35 vs 5.22 ± 0.92,p = 0.02;和 100 J)中,对照和 PIT 治疗的肿瘤之间的 ICG 强度存在统计学差异(p < 0.05) cm(-2) : 3.56 ± 0.96 vs 5.71 ± 1.43, p = 0.008) 早在 ICG 注射后 20 分钟。然而,在低光照组中,在长达 60 分钟的任何时间点(10 J cm(-2) : 1.92 ± 0.49 vs 1.71 ± 0.3, p = 0.44; 和 30 J cm(-2): 1.57 ± 0.35 vs 2.75 ± 0.59, p = 0.07)。同样,保留指数(背景与 ICG 校正摄取比)随光照变化。综上所述,
更新日期:2019-11-01
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