Tissue distribution and photosensitizing properties of mono-L-aspartyl chlorin e6 in a mouse tumor model.
Tissue distribution and photosensitizing properties of mono-L-aspartyl chlorin e6 in a mouse tumor model.
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发表时间：
1990-07
期刊：
影响因子：
11.2
通讯作者：
C. Gomer;A. Ferrario
中科院分区：
文献类型：
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作者：
C. Gomer;A. Ferrario
单-L-乙酰基二氢卟酚e6（NPe 6）是一种光敏剂，其具有诸如化学纯度和在664 nm处的主要吸收带的性质，其潜在地可用于光动力疗法（PDT）。目前的研究检查了NPe 6在小鼠肿瘤和正常组织中的药理学和光敏化参数。[14 C] NPe 6用于获得光敏剂的定量组织分布，其为：（a）给药后时间;（B）药物剂量;（c）给药方式;和（d）肿瘤大小的函数。在评价肿瘤反应和诱导正常皮肤损伤的实验中，将NPe 6的体内光敏化效率直接与Photofrin II进行比较。最初的PDT实验表明，当使用24小时的时间间隔（在药物施用和光治疗之间）时，NPe 6在诱导肿瘤治愈方面是无效的。然而，当在光暴露之前4-6小时施用NPe 6时，获得PDT诱导的肿瘤治愈，并且这些NPe 6-PDT治疗参数与标准Photofrin II介导的PDT一样有效。有趣的是，在相当的药物和光剂量下，Photofrin II的PDT诱导的正常皮肤损伤水平显著高于NPe 6。对药理学数据和PDT时间间隔要求的分析表明，对于PDT介导的肿瘤治疗的产生，NPe 6的血浆浓度可能是比光敏剂的肿瘤组织水平更重要的预测因素。本研究的结果表明，NPe 6是一种有效的肿瘤光敏剂，具有体内清除特性，消除了延长正常皮肤光敏化的副作用。
Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm which are potentially exploitable for photodynamic therapy (PDT). The current investigation examined pharmacological and photosensitizing parameters of NPe6 in tumor and normal tissues in mice. [14C]NPe6 was used to obtain quantitative tissue distributions of the photosensitizer as a function of: (a) time following administration; (b) drug dose; (c) mode of drug administration; and (d) tumor size. The in vivo photosensitizing efficiency of NPe6 was compared directly to Photofrin II in experiments which evaluated tumor responses and induction of normal skin damage. Initial PDT experiments demonstrated that NPe6 was ineffective at inducing tumor cures when a 24-h time interval (between drug administration and light treatment) was used. However, PDT-induced tumor cures were obtained when NPe6 was administered 4-6 h prior to light exposure, and these NPe6-PDT treatment parameters were as effective as standard Photofrin II-mediated PDT. Interestingly, the level of PDT-induced normal skin damage was significantly greater for Photofrin II than for NPe6 at comparable drug and light doses. An analysis of pharmacological data and PDT time interval requirements suggests that plasma concentrations of NPe6 may be a more important predictive factor than tumor tissue levels of the photosensitizer for the production of PDT-mediated tumor cures. The results of this investigation indicate that NPe6 is an effective tumor photosensitizer with in vivo clearance properties that eliminate the side effect of prolonged normal skin photosensitization.