2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-α (HPPH) in a nude rat glioma model:: Implications for photodynamic therapy
2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-α (HPPH) in a nude rat glioma model:: Implications for photodynamic therapy
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DOI：
10.1002/lsm.10001
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发表时间：
2001-01-01
影响因子：
2.4
通讯作者：
Dougherty, TJ
中科院分区：
文献类型：
--
作者：
Lobel, J;MacDonald, IJ;Dougherty, TJ
背景和目的：在本研究中，我们评估了 2-[1-己氧基乙基]-2-脱乙烯基焦脱镁叶绿酸-α（HPPH 或光氯）作为光敏剂用于通过光动力疗法 (PDT) 治疗恶性胶质瘤。研究设计/材料和方法：我们在无胸腺大鼠中进行了体内反射光谱，以测量正常脑组织中光的衰减。我们还研究了 HPPH 药代动力学和 PDT 对患有立体定向植入 U87 人胶质瘤细胞脑肿瘤的裸鼠的影响。在指定时间点处死植入肿瘤的大鼠，测定HPPH在血清、肿瘤、正常脑和肿瘤邻近脑（BAT）中的药代动力学。使用荧光光谱法测定正常脑、BAT 和肿瘤中的 HPPH 浓度。静脉注射 HPPH 24 小时后，我们在 665 nm 波长下进行间质 PDT 治疗。在肿瘤部位以 3.5、7.5 或 15 J/cm2 的剂量和 50 mW/cm2 的速率给予光。结果：正常脑组织的体内光谱显示，665 nm 光的衰减深度与用于激活 Photofrin 的 630 nm 光的衰减深度相似，大 30%，目前正在评估光动力疗法作为恶性神经胶质瘤手术辅助剂的 PDT。药物从血清和肿瘤中消失的t 1/2 分别为25和30小时。结论：注射0.5 mg/kg HPPH后24小时，肿瘤与脑的药物比例范围为5:1至15:1。在每个 HPPH/PDT 治疗的动物组中都观察到存活率提高。这些数据表明 HPPH 可能是治疗恶性神经胶质瘤的有用佐剂。激光外科。医学。 29:397-405, 2001。(C) 2001 Wiley-Liss, Inc.
Background and Objective: In this study, we evaluated 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha (HPPH or Photochlor) as a photosensitizer for the treatment of malignant gliomas by photodynamic therapy (PDT).Study Design/Materials and Methods: We performed in vivo reflection spectroscopy in athymic rats to measure the attenuation of light in normal brain tissue. We also studied HPPH pharmacokinetics and PDT effects in nude rats with brain tumors derived from stereotactically implanted U87 human glioma cells. Rats implanted with tumors were sacrificed at designated time points to determine the pharmacokinetics of HPPH in serum, tumor, normal brain, and brain adjacent to tumor (BAT). HPPH concentrations in normal brain, BAT and tumor were determined using fluorescence spectroscopy. Twenty-four hours after intravenous injection of HPPH, we administered interstitial PDT treatment at a wavelength of 665 nm. Light was given in doses of 3.5, 7.5 or 15 J/cm at the tumor site and at a rate of 50 mW/cm.Results: In vivo spectroscopy of normal brain tissue showed that the attenuation depth of 665 nm light is similar to 30% greater than that of 630 nm light used to activate Photofrin, which is currently being evaluated for PDT as an adjuvant to surgery for malignant gliomas. The t 1/2 of disappearance of drug from serum and tumor was 25 and 30 hours, respectively.Conclusion: Twenty-four hours after injection of 0.5 mg/kg HPPH, tumor-to-brain drug ratios ranged from 5:1 to 15:1. Enhanced survival was observed in each of the HPPH/PDT-treated animal groups. These data suggest that HPPH may be a useful adjuvant for the treatment of malignant gliomas. Lasers Surg. Med. 29:397-405, 2001. (C) 2001 Wiley-Liss, Inc.