近红外光免疫疗法（NIR-PIT）是一种有前景的癌症治疗方法，结合了近红外光辐射、抗体和IR700DX，一种光敏感物质，用于摧毁肿瘤。然而，均匀辐照是困难的，因为光线根据距离和组织环境的不同而变化。因此，需要标记指示足够辐射的标记物。纳米粒子的尺寸在10∼200 nm之间，在肿瘤内表现出增强的渗透和积聚作用，通过NIR-PIT进一步增强（超增强渗透和积聚，SUPR）。我们的目标是通过测量SUPR来监测NIR-PIT的有效性。通过将人源癌细胞接种在Balb/C-nu/nu小鼠的两侧臀部建立异种移植物小鼠肿瘤模型，并仅对一侧进行NIR-PIT。为了评估SUPR，使用QD800荧光纳米粒子和近红外荧光聚（d，l-乳酸-羟基乳酸）（NIR-PLGA）微粒进行荧光信号检测。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。评估了治疗后立即的SUPR与治疗后一天的NIR-PIT有效性之间的相关性。QD800荧光信号仅在治疗肿瘤中持续存在，并且剩余信号的强度与治疗效果呈高正相关。与对照组相比，NIR-PLGA荧光信号和Sonazoid源谐波信号在治疗肿瘤中的存在时间更长，两室模型的kE值与NIR-PIT的有效性呈相关性。使用Sonazoid和CEUS成像来测量SUPR，可以很容易地用于临床，作为监测和确认NIR-PIT疗效的治疗图像生物标记物。本研究得到了ARIM JAPAN（MEXT）、下一代研究员培养计划（日本科学技术振兴机构）、KAKEN（18K15923，21K07217）（JSPS）、CREST（JPMJCR19H2，JST）和FOREST-Souhatsu（JST）的支持。本研究的资助者仅提供财务支持，并不参与研究设计、数据收集、数据分析、解释和报告编写。版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。

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.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.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.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.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.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.