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.
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。