PDF(Pubmed)
Abstract：
BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy combining NIR-light irradiation with an antibody and IR700DX, a light-sensitive substance, to destroy tumours. However, homogeneous irradiation is difficult because the light varies depending on the distance and tissue environment. Therefore, markers that indicate sufficient irradiation are necessary. Nanoparticles sized 10∼200 nm show enhanced permeation and retention within tumours, which is further enhanced via NIR-PIT (super enhanced permeability and retention, SUPR). We aimed to monitor the effectiveness of NIR-PIT by measuring SUPR.
METHODS: A xenograft mouse tumour model was established by inoculating human cancer cells in both buttocks of Balb/C-nu/nu mice, and NIR-PIT was performed on only one side. To evaluate SUPR, fluorescent signal examination was performed using QD800-fluorescent nanoparticles and NIR-fluorescent poly (d,l-lactide-co-glycolic acid) (NIR-PLGA) microparticles. Harmonic signals were evaluated using micro-bubbles of the contrast agent Sonazoid and contrast-enhanced ultrasound (CEUS) imaging. The correlation between SUPR immediately after treatment and NIR-PIT effectiveness on the day after treatment was evaluated.
RESULTS: QD800 fluorescent signals persisted only in the treated tumours, and the intensity of remaining signals showed high positive correlation with the therapeutic effect. NIR-PLGA fluorescent signals and Sonazoid-derived harmonic signals remained for a longer time in the treated tumours than in the controls, and the kE value of the two-compartment model correlated with NIR-PIT effectiveness.
CONCLUSIONS: SUPR measurement using Sonazoid and CEUS imaging could be easily adapted for clinical use as a therapeutic image-based biomarker for monitoring and confirming of NIR-PIT efficacy.
BACKGROUND: This research was supported by ARIM JAPAN of MEXT, the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, 21K07217) (JSPS), CREST (JPMJCR19H2, JST), and FOREST-Souhatsu (JST). Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; and Princess Takamatsu Cancer Research Fund. Funders only provided financial support and had no role in the study design, data collection, data analysis, interpretation, and writing of the report.
METHODS: A xenograft mouse tumour model was established by inoculating human cancer cells in both buttocks of Balb/C-nu/nu mice, and NIR-PIT was performed on only one side. To evaluate SUPR, fluorescent signal examination was performed using QD800-fluorescent nanoparticles and NIR-fluorescent poly (d,l-lactide-co-glycolic acid) (NIR-PLGA) microparticles. Harmonic signals were evaluated using micro-bubbles of the contrast agent Sonazoid and contrast-enhanced ultrasound (CEUS) imaging. The correlation between SUPR immediately after treatment and NIR-PIT effectiveness on the day after treatment was evaluated.
RESULTS: QD800 fluorescent signals persisted only in the treated tumours, and the intensity of remaining signals showed high positive correlation with the therapeutic effect. NIR-PLGA fluorescent signals and Sonazoid-derived harmonic signals remained for a longer time in the treated tumours than in the controls, and the kE value of the two-compartment model correlated with NIR-PIT effectiveness.
CONCLUSIONS: SUPR measurement using Sonazoid and CEUS imaging could be easily adapted for clinical use as a therapeutic image-based biomarker for monitoring and confirming of NIR-PIT efficacy.
BACKGROUND: This research was supported by ARIM JAPAN of MEXT, the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, 21K07217) (JSPS), CREST (JPMJCR19H2, JST), and FOREST-Souhatsu (JST). Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; and Princess Takamatsu Cancer Research Fund. Funders only provided financial support and had no role in the study design, data collection, data analysis, interpretation, and writing of the report.
摘要：
背景：近红外光免疫疗法（NIR-PIT）是一种将NIR光照射与抗体和IR700DX相结合的有前途的癌症疗法，一种光敏物质，摧毁肿瘤。然而,均匀的照射是困难的，因为光的变化取决于距离和组织环境。因此,表明足够辐照的标记是必要的。大小为10~200nm的纳米颗粒在肿瘤内显示出增强的渗透和保留，通过NIR-PIT(超增强渗透率和保留率，SUPR)。我们旨在通过测量SUPR来监测NIR-PIT的有效性。
方法：通过在Balb/C-nu/nu小鼠的两个臀部接种人癌细胞，建立异种移植小鼠肿瘤模型，NIR-PIT仅在一侧进行。要评估SUPR，使用QD800-荧光纳米粒子和NIR-荧光聚（d，1-丙交酯-共-乙醇酸)(NIR-PLGA)微粒。使用造影剂Sonazoid的微泡和对比增强超声（CEUS）成像评估谐波信号。评估治疗后即刻的SUPR与治疗后当天的NIR-PIT有效性之间的相关性。
结果：QD800荧光信号仅在治疗的肿瘤中持续存在，其余信号强度与治疗效果呈高度正相关。与对照组相比，NIR-PLGA荧光信号和Sonazoid衍生的谐波信号在治疗的肿瘤中保留的时间更长，两室模型的kE值与NIR-PIT有效性相关。
结论：使用Sonazoid和CEUS成像的SUPR测量可以很容易地适应临床应用，作为基于治疗图像的生物标志物，用于监测和确认NIR-PIT疗效。
背景：这项研究得到了MEXT的ARIMJAPAN的支持，开发下一代研究人员计划（日本科学技术厅），KAKEN(18K15923,21K07217)(JSPS),CREST(JPMJCR19H2,JST),和FOREST-Souhatsu（JST）。Mochida医学和药物研究纪念基金会；武田科学基金会；日本健康基金会；和高松公主癌症研究基金会。资助者仅提供财政支持，在研究设计中没有任何作用，数据收集，数据分析,解释,和撰写报告。
方法：通过在Balb/C-nu/nu小鼠的两个臀部接种人癌细胞，建立异种移植小鼠肿瘤模型，NIR-PIT仅在一侧进行。要评估SUPR，使用QD800-荧光纳米粒子和NIR-荧光聚（d，1-丙交酯-共-乙醇酸)(NIR-PLGA)微粒。使用造影剂Sonazoid的微泡和对比增强超声（CEUS）成像评估谐波信号。评估治疗后即刻的SUPR与治疗后当天的NIR-PIT有效性之间的相关性。
结果：QD800荧光信号仅在治疗的肿瘤中持续存在，其余信号强度与治疗效果呈高度正相关。与对照组相比，NIR-PLGA荧光信号和Sonazoid衍生的谐波信号在治疗的肿瘤中保留的时间更长，两室模型的kE值与NIR-PIT有效性相关。
结论：使用Sonazoid和CEUS成像的SUPR测量可以很容易地适应临床应用，作为基于治疗图像的生物标志物，用于监测和确认NIR-PIT疗效。
背景：这项研究得到了MEXT的ARIMJAPAN的支持，开发下一代研究人员计划（日本科学技术厅），KAKEN(18K15923,21K07217)(JSPS),CREST(JPMJCR19H2,JST),和FOREST-Souhatsu（JST）。Mochida医学和药物研究纪念基金会；武田科学基金会；日本健康基金会；和高松公主癌症研究基金会。资助者仅提供财政支持，在研究设计中没有任何作用，数据收集，数据分析,解释,和撰写报告。
