Activating Photodynamic Therapy in vitro with Cerenkov Radiation Generated from Yttrium-90.
Activating Photodynamic Therapy in vitro with Cerenkov Radiation Generated from Yttrium-90.
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DOI：
10.1615/jenvironpatholtoxicoloncol.2016016903
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Cherry SR
中科院分区：
文献类型：
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作者：
Hartl BA;Hirschberg H;Marcu L;Cherry SR
光动力疗法（PDT）在临床环境中的应用主要局限于易接触和/或浅表疾病，传统的光输送可以无创地进行。切伦科夫辐射是由医学上相关的放射性核素产生的，已被建议作为一种将光无创地传递到更深的组织以克服这种深度限制的手段。本文研究了切伦科夫辐射（由放射性核素钇-90产生）在临床批准的1.0 mm的氨基乙酰酸和1.2 μM的相邻苯基环（TPPS2a）上具有两个磺酸基的卟啉基光敏剂介四苯基卟啉（mesotetraphenylporphine）激活PDT过程中的效用。用单层培养的胶质瘤细胞系和乳腺肿瘤细胞系进行了实验。尽管在最高活性水平下，氨基乙酰丙酸不能产生治疗效果，但TPPS2a在6至60 μCi/孔的活性范围内对C6胶质瘤细胞系产生至少20%的治疗效果。重要的是，据我们所知，这些结果首次证明，放射性核素产生的切伦科夫辐射可以使用临床相关的光敏剂来激活PDT。因此，这些结果提供了证据，证明使用切伦科夫辐射和临床相关光敏剂可能在体内产生光疗效果。
The translation of photodynamic therapy (PDT) to the clinical setting has primarily been limited to easily accessible and/or superficial diseases, for which traditional light delivery can be performed noninvasively. Cerenkov radiation, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively to overcome this depth limitation. This article investigates the utility of Cerenkov radiation, as generated from the radionuclide yttrium-90, for activating the PDT process using clinically approved aminolevulinic acid at 1.0 mm and also the more efficient porphyrin-based photosensitizer mesotetraphenylporphine with two sulfonate groups on adjacent phenyl rings (TPPS2a) at 1.2 μM. Experiments were conducted with monolayer cultured glioma and breast tumor cell lines. Although aminolevulinic acid proved to be ineffective for generating a therapeutic effect at all but the highest activity levels, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 μCi/well for the C6 glioma cell line. Importantly, these results demonstrate for the first time, to our knowledge, that Cerenkov radiation generated from a radionuclide can be used to activate PDT using clinically relevant photosensitizers. These results therefore provide evidence that it may be possible to generate a phototherapeutic effect in vivo using Cerenkov radiation and clinically relevant photosensitizers.