Lobel J, MacDonald I J, Ciesielski M J, Barone T, Potter W R, Pollina J, Plunkett R J, Fenstermaker R A, Dougherty T J
Department of Neurosurgery, State University of New York School of Medicine and Biomedical Sciences, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Lasers Surg Med. 2001;29(5):397-405. doi: 10.1002/lsm.10001.
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.
In vivo spectroscopy of normal brain tissue showed that the attenuation depth of 665 nm light is approximately 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 t1/2 of disappearance of drug from serum and tumor was 25 and 30 hours, respectively.
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.
在本研究中，我们评估了2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-α（HPPH或光氯）作为一种用于光动力疗法（PDT）治疗恶性胶质瘤的光敏剂。
研究设计/材料与方法：我们在无胸腺大鼠中进行体内反射光谱分析，以测量正常脑组织中光的衰减情况。我们还研究了HPPH在源自立体定向植入U87人胶质瘤细胞的脑肿瘤裸鼠中的药代动力学及PDT效应。在指定时间点处死植入肿瘤的大鼠，以确定HPPH在血清、肿瘤、正常脑及肿瘤邻近脑（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50 mW/cm的速率给予3.5、7.5或15 J/cm的光剂量。
正常脑组织的体内光谱分析表明，665 nm光的衰减深度比用于激活目前正在评估作为恶性胶质瘤手术辅助治疗的光卟啉的630 nm光大约大30%。药物从血清和肿瘤中消失的t1/2分别为25小时和30小时。
注射0.5 mg/kg HPPH 24小时后，肿瘤与脑的药物比率在5:1至15:1之间。在每个接受HPPH/PDT治疗的动物组中均观察到生存期延长。这些数据表明，HPPH可能是治疗恶性胶质瘤的一种有用辅助药物。
