WST11, a novel water-soluble bacteriochlorophyll derivative; Cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model
WST11, a novel water-soluble bacteriochlorophyll derivative; Cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model
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DOI：
10.1562/2004-06-14-ra-199.1
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Scherz, A
中科院分区：
文献类型：
--
作者：
Mazor, O;Brandis, A;Scherz, A
WST 11是一种新型的带负电荷的水溶性钯-细菌叶绿素衍生物，是我们实验室开发的用于血管靶向光动力治疗（VTP）的药物。体外实验结果表明，WST 11细胞的摄取、清除和光毒性是由血清白蛋白转运介导的。在体内，发现WST 11在小鼠中静脉推注后从循环中快速清除（t（1/2）= 1.65 min），而在大鼠中在输注20 min后观察到较长的清除时间（t（1/2）= 7.5 min）。WST 11在小鼠组织中的生物分布表明肝脏清除（t（1/2）= 20 min），在其他组织中有少量（肾、肺和脾）或无中间蓄积。注射后1小时，WST 11几乎从小鼠体内清除，除了在肺部的时间积累，它在40分钟内清除。在这些结果的基础上，我们设置了一个短的照明时间（5分钟）的VTP协议，WST 11注射后立即交付。在对M2 R黑色素瘤异种移植物进行WST 11-VTP时，我们在所有剂量下实现了100%的肿瘤扁平化，并且在9 mg/kg和100 mW/cm 2的光暴露剂量下实现了70%的治愈。这些结果提供了直接的证据，WST 11是一个有效的代理商的VTP，并提供指导方针，为进一步开发新的候选人。
WST11 is a novel negatively charged water-soluble palladium-bacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t(1/2) = 1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t(1/2) = 7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t(1/2) = 20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm(2). These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.