Photodynamic therapy and diagnosis of5-aminolevulinic acid for gastrointestinal cancer

5-氨基乙酰丙酸治疗消化道肿瘤的光动力治疗及诊断

基本信息

批准号：
16591309
负责人：
TANAKA Tatsuo
金额：
$ 2.24万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Photofrin is the most commonly used photosensitizer for photodynamic therapy (PDT). The major side effect of Photofrin is cutaneous photosensitivity. 5-aminolevulinic acid (5-ALA) is potentially exploitable for PDT and does not cause the side effect of prolonged normal skin photosensitization. We investigated the anti-tumor effects and safety of 5-ALA in patients with gastrointestinal cancer. 5-ALA(30 mg/kg) was administrated orally. At 4 h after administration, laser beam was irradiated to the tumor site endscopically using a directional quartz fiber (energy level : 100 J/cm^2). The antitumor effects of 5-ALA PDT according to patients were one PR and two SD. We investigated antitumor effects of 5-ALA PDT for human gastric cancer by animal model. Nude mice were implanted subcutaneously MT2 tumor (human gastric cancer line) and 5-ALA PDT was done. The rates of tumor shrinkage after PDT were 0.40 (5-ALA) and 0.16 (Photofrin). Judging from these results, anti-tumor effect of 5-ALA PDT is not satisfaction in the clinical and basic research.Next, we investigated antitumor effects of PDT using a fractionated dosing of mono-L-aspartyl chlorine e6 (NPe6) in a murine tumor. Eight nude mice with MT2 tumor were given 10 mg/kg NPe6 intravenously. Two hours later PDT was performed using a laser diode at a light dose of 100 J/ cm^2 and wavelength of 664 nm. Histological changes in tumors were examined 3 weeks after PDT. The CR rate was 87.5 % and the overall response rate was 100 %. The anti-tumor efficacy of NPe6 for human gastric cancer is very excellent correspond to it of Photofrin.

光蛋白是光动力疗法（PDT）最常用的光敏剂。光蛋白的主要副作用是皮肤光敏性。 5-氨基乙烯酸（5-ALA）可能可用于PDT，并且不会引起长时间正常皮肤光敏化的副作用。我们研究了5-ALA对胃肠癌患者的抗肿瘤作用和安全性。 5-ALA（30 mg/kg）口服管理。给药后4小时，激光束使用定向石英纤维（能级：100 J/cm^2）将激光束辐射到肿瘤部位。根据患者的5-ALA PDT的抗肿瘤作用是1个PR和两个SD。我们通过动物模型研究了5-ALA PDT对人胃癌的抗肿瘤作用。裸鼠是皮下植入MT2肿瘤（人胃癌系），并进行了5-ALA PDT。 PDT后肿瘤收缩率为0.40（5-ALA）和0.16（光蛋白）。从这些结果来看，5-ALA PDT的抗肿瘤效应在临床和基础研究中不满意。接下来，我们使用鼠类肿瘤中单氯 - 甲基氯E6（NPE6）的分馏来研究了PDT的抗肿瘤作用。静脉注射八只具有MT2肿瘤的裸小鼠10 mg/kg NPE6。两个小时后，使用激光二极管以100 j/ cm^2的光剂量和664 nm的波长进行PDT。 PDT后3周检查了肿瘤的组织学变化。 CR率为87.5％，总体响应率为100％。 NPE6对人胃癌的抗肿瘤功效非常出色，与光蛋白的抗肿瘤功效相对应。