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Dynamic fluorescent imaging with indocyanine green for monitoring the therapeutic effects of photoimmunotherapy

机译:用吲哚菁绿进行动态荧光成像以监测光免疫疗法的治疗效果

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A new type of monoclonal antibody (mAb)a??based, highly specific phototherapy (photoimmunotherapy; PIT) that uses a neara??infrared (NIR) phthalocyanine dye, IRDye700DX (IR700) conjugated with an mAb, has recently been described. NIR light exposure leads to immediate, targeta??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 EGFRa??expressing A431 tumor cells and in vivo xenografts. PIT was performed at varying doses of NIR light (10, 30, 50 and 100a??Ja??cma??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 (pa??a??0.05) in ICG intensity between control and PIT treated tumors in the higher light exposure groups (50a??Ja??cma??2: 2.94a???±a??0.35 vs 5.22a???±a??0.92, pa??=a??0.02; and 100a??Ja??cma??2: 3.56a???±a??0.96 vs 5.71a???±a??1.43, pa??=a??0.008) as early as 20a??min post ICG injection. However, no significant difference (pa??a??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 60a??min (10a??Ja??cma??2: 1.92a???±a??0.49 vs 1.71a???±a??0.3, pa??=a??0.44; and 30a??Ja??cma??2: 1.57a???±a??0.35 vs 2.75a???±a??0.59, pa??=a??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 mAba??IR700a??induced PIT even before morphological changes can be seen in targeted tumors. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.
机译:最近已经描述了一种新型的基于单克隆抗体(mAb)α-的高特异性光疗(光免疫疗法; PIT),其使用与mAb结合的近红外(NIR)酞菁染料IRDye700DX(IR700)。近红外光照射导致立即的靶标选择性坏死细胞死亡。但是,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结合的表皮生长因子受体(EGFR1)的帕尼单抗被用于治疗表达EGFRaβ的A431肿瘤细胞和体内异种移植物。在小鼠的异种移植肿瘤中以不同剂量的NIR光(10、30、50和100aΔαΔαcmaΔ2)进行PIT。吲哚菁绿(ICG)动态成像进行了评估,以监测PIT后第一小时的细胞毒性作用。我们的结果表明,在较高光照组中,对照和PIT治疗的肿瘤之间ICG强度的统计学差异(pa ?? ?? 0.05)(50a?Ja?cma?2:2.94a?±a) 0.35vs 5.22a +/-±a 0.92,pa = a 0.02;和100aΔω-1 cmaε2:3.56a +/-±a 0.96 vs 5.71a?早在ICG注射后20a -1分钟,Δα±aΔ1.43,paΔ= aΔ0.008)。但是,在低照度组中,在长达60a·min的任何时间点(10a·α-1·Ja·cma)的任何时间点,对照组和PIT治疗的肿瘤之间的ICG强度均无明显差异(pa ??> a ?? 0.05)。 △2:1.92a△±a△0.49与1.71a△±a△0.3,pa△= a△0.44;和30a△Ja△cma△2:1.57a? Δα±αΔ0.35与2.75aΔ±αΔ0.59,paΔα=aΔβ0.07)。同样,保留指数(ICG的本底与校正后的摄取率)随曝光量而变化。总之,甚至在目标肿瘤形态学改变尚未见到的情况下,ICG仍可作为mAbaβIR700aβ诱导的PIT急性细胞毒性作用的潜在指标。 2014年出版。本文是美国政府的工作,在美国属于公共领域。

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