Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC

Experimental photodynamic therapy for malignant pleural mesothelioma with pegylated mTHPC
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DOI:
10.1002/lsm.10113
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发表时间:
2003-01-01
影响因子:
2.4
通讯作者:
Ris, HB
Ris, HB
中科院分区:
医学3区
文献类型:
--
作者:
Krueger, T;Altermatt, HJ;Ris, HB

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背景和目的:使用间四羟基苯基二氯甲烷的聚乙二醇缀合物 (PEG-mTHPC) 对恶性胸膜间皮瘤的光动力疗法 (PDT) 进行实验评估。研究设计/材料和方法:(a) 在 H-meso-1 异种移植物上测试 PDT(652 nm 激光;注量 10 j/cm(2);0.93、9.3 或 27.8) mg/kg PEG-mTHPC;药物光照间隔 3-8 天)。 (b) 采用光学积分球囊装置结合原位光剂量测定,对小型猪 (n = 18) 胸膜外肺切除术 (EPP) 后的胸腔进行类似治疗条件的术中 PDT。结果:(a) 使用 PEG-mTHPC 的 PDT 导致肿瘤坏死范围比未治疗的肿瘤更大(P 小于或等于 0.01),且不会对正常组织造成损伤。 (b) 18 只动物中有 17 只对 EPP 后的术中 PDT 耐受性良好。在胸腔四个部位测量的平均注量和注量率范围为 10.2 +/- 0.2 至 13.2 +/- 2.3 J/cm(2) 和 5.5 +/- 1.2 至 7.9 +/- 1.7 mW/cm(2)(平均值 +/- SD)。光照射后3个月的组织学显示,除一只动物外,所有动物均未出现与PDT相关的组织损伤。结论:在相似的治疗条件下,PEG-mTHPC介导的PDT显示出对间皮瘤异种移植物的选择性破坏,而不会对猪的胸内器官造成损害。光传输系统向胸腔的不同部位提供规则的光分布。 (C) 2003 Wiley-Liss, Inc.
Background and Objectives: Experimental assessment of photodynamic therapy (PDT) for malignant pleural mesothelioma using a polyethylene glycol conjugate of meta-tetrahydroxyphenylchlorin (PEG-mTHPC).Study Design/Materials and Methods: (a) PDT was tested on H-meso-1 xenografts (652 nm laser light; fluence 10 j/cm(2); 0.93, 9.3, or 27.8 mg/kg of PEG-mTHPC; drug-light intervals 3-8 days). (b) Intraoperative PDT with similar treatment conditions was performed in the chest cavity of minipigs (n = 18) following extrapleural pneumonectomy (EPP) using an optical integrating balloon device combined with in situ light dosimetry.Results: (a) PDT using PEG-mTHPC resulted in larger extent of tumor necrosis than in untreated tumors (P less than or equal to 0.01) without causing damage to normal tissue. (b) Intraoperative PDT following EPP was well tolerated in 17 of 18 animals. Mean fluence and fluence rates measured at four sites of the chest cavity ranged from 10.2 +/- 0.2 to 13.2 +/- 2.3 J/cm(2) and 5.5 +/- 1.2 to 7.9 +/- 1.7 mW/cm(2) (mean +/- SD). Histology 3 months after light delivery revealed no PDT related tissue injury in all but one animal.Conclusions: PEG-mTHPC mediated PDT showed selective destruction of mesothelioma xenografts without causing damage to intrathoracic organs in pigs at similar treatment conditions. The light delivery system afforded regular light distribution to different parts of the chest cavity. (C) 2003 Wiley-Liss, Inc.