Intratumor Administration of the Photosensitizer Pc 4 Affords Photodynamic Therapy Efficacy and Selectivity at Short Drug-Light Intervals
Intratumor Administration of the Photosensitizer Pc 4 Affords Photodynamic Therapy Efficacy and Selectivity at Short Drug-Light Intervals
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DOI：
10.1593/tlo.09295
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发表时间：
2010-04-01
影响因子：
5
通讯作者：
Mitra, Soumya
中科院分区：
文献类型：
--
作者：
Foster, Thomas H.;Giesselman, Benjamin R.;Mitra, Soumya
我们评价了肿瘤内（IT）与静脉（IV）给药的光敏剂Pc 4的肿瘤光敏剂浓度，特异性和对辐射的反应。BALB/c小鼠皮下移植EMT 6肿瘤，经尾静脉注射Pc 4 0.3mg/kg。通过氯仿提取评价光敏剂浓度，并通过体内荧光成像和光谱学评估定位。在667 nm、50 mW/cm（2）和100 J/cm（2）下照射肿瘤。治愈定义为照射后90天无明显肿瘤。IT给药后1小时的肿瘤Pc 4浓度是IV给药后24小时测量值的35，000倍（0.112 vs 0.317 x 10 - 5 μ g Pc 4/mg肿瘤）。在IT注射后1小时观察到极好的肿瘤选择性。新鲜切片的肿瘤的荧光成像显示在该时间点没有缺乏敏化剂的区域，中线切片中的像素强度在峰值强度的3倍内。对于相同的光敏剂剂量，IT管理显着改善肿瘤对辐射的反应，超过70%的肿瘤治愈IT-Pc 4-PDT。在该模型中，IT-Pc 4给药提供了改善的肿瘤控制、更大的选择性和短的药物-光间隔的机会。
We evaluated intratumor (IT) versus intravenous (IV) administration of the photosensitizer Pc 4 with respect to tumor photosensitizer concentration, specificity, and responses to irradiation. BALB/c mice bearing intradermal EMT6 tumors were given 0.3 mg/kg Pc 4 injected IT or IV through the tail vein. Photosensitizer concentration was evaluated by chloroform extraction and localization assessed by fluorescence imaging and spectroscopy in vivo. Tumors were irradiated at 667 nm, 50 mW/cm(2), and 100 J/cm(2). Cures were defined as no palpable tumor 90 days after irradiation. Tumor Pc 4 concentrations 1 hour after IT administration were 35,000-fold higher than measured 24 hours after IV administration (0.112 vs 0.317 x 10(-5) mu g Pc 4/mg tumor). Exquisite tumor selectivity was observed 1 hour after IT injection. Fluorescence imaging of freshly sectioned tumors revealed no regions devoid of sensitizer at this time point, with pixel intensities in a midline section within a factor of 3 of the peak intensity. For identical photosensitizer doses, IT administration significantly improved tumor responses to irradiation, with more than 70% of tumors cured with IT-Pc 4-PDT. In this model, IT-Pc 4 administration provides improved tumor control, greater selectivity, and opportunity for a short drug-light interval.