Biodistribution and Pharmacokinetic Studies of a Porphyrin Dimer Photosensitizer (Oxdime) by Fluorescence Imaging and Spectroscopy in Mice Bearing Xenograft Tumors

Biodistribution and Pharmacokinetic Studies of a Porphyrin Dimer Photosensitizer (Oxdime) by Fluorescence Imaging and Spectroscopy in Mice Bearing Xenograft Tumors
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通过荧光成像和光谱学研究卟啉二聚体光敏剂 (Oxdime) 在携带异种移植肿瘤的小鼠中的生物分布和药代动力学

DOI:
10.1111/j.1751-1097.2012.01194.x
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发表时间:
2012
影响因子:
3.3
通讯作者:
Khurana M
Khurana M
中科院分区:
生物学3区
文献类型:
--
作者:
Khurana M

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在此,我们提出了一项丁二炔连接的共轭卟啉二聚体(Oxdime)的药代动力学和生物分布研究,该二聚体设计用于光动力学治疗(PDT),具有高近红外(NIR)双光子吸收截面。在静脉注射后,在携带B16-F10黑素瘤异种移植物的小鼠中监测生物分布随时间的变化。使用活体动物的荧光成像和分析注射后30min和24 h之间的不同时间点的分离的器官活体,测量了Oxdime在几个器官(心脏、肾脏和肝脏)和肿瘤中的积累。 血浆中的浓度比其他组织中的浓度高约5-10倍。在大多数组织中,包括肿瘤和血浆中,荧光信号在注射后3-12 h达到峰值。还监测了敏化剂的荧光发射光谱随时间的变化,并在24小时内观察到最大值从800 nm偏移至740 nm,表明Oxdime被代谢。  在肿瘤中积累了大量,表明这种PDT敏化剂可能有希望用于癌症治疗。
Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne‐linked conjugated porphyrin dimer (Oxdime) designed to have high near‐infrared (NIR) 2‐photon absorption cross‐section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16‐F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organsex vivoat different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5–10 times higher than in other tissues. The fluorescence signal peaked at 3–12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment.
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