HPPH光敏剂不同时段在颅内外肿瘤、正常脑及皮肤组织间的代谢分布

The Metabolism of HPPH on Brain and Tumor and Skin of Mice G422 Glioma

目的:观察静脉注射不同剂量HPPH光敏剂后不同时段透过血脑屏障在颅内外肿瘤与正常脑组织、皮肤间的代谢分布,并确定静脉注射HPPH光敏剂后在脑胶质瘤高浓度聚集与正常组织大部份排出相差距离最大的时间段,为光敏诊断、光动力治疗提供最佳时间及剂量。方法:建立鼠G422脑胶质瘤、腋部皮下移植瘤模型,设立注射HPPH 0.15mg/kg组、HPPH 0.3mg/kg组、HPPH 0.45mg/kg组、以荧光图像早期癌诊断仪测定注药前、注药后(4、8、12、18、24、32、48h)肿瘤及正常脑组织、皮肤、口腔及眼粘膜的荧光峰值,选择在肿瘤中有较高的HPPH浓度,正常脑组织及皮肤大部分已排出的最大距离值,以确定HPPHPDT,HPPH注药后最佳的诊断、治疗时间及剂量。结果:从鼠G422脑胶质瘤、腋部皮下移植瘤模型注HPPH 0.15mg/kg组、HPPH 0.3mg/kg组、HPPH 0.45mg/kg组、以荧光图像早期癌诊断仪测定注药前、注药后(4、8、12、18、24、32、48h)不同时间脑肿瘤、腋部皮下肿瘤、正常脑、正常皮肤、口腔及眼粘膜的荧光峰值看,HPPH在注药后12～24h时正常组织荧光峰已较低,而肿瘤尚有较高的荧光峰,二者的距离也较大,是作荧光诊断及光动力学治疗的较佳时间,HPPH 0.3mg/kg、HPPH 0.45mg/kg组峰值平均值接近,并稍高于HPPH 0.15mg/kg组,故HPPH注药0.3mg/kg、注药后12～24h是作鼠G422脑胶质瘤肿瘤光敏诊断及光动力学治疗的较佳剂量及时间,三组注药后口腔及眼粘膜的荧光峰值均较高,且48h仍有较高的浓度,应注意口、眼在HPPH-PDT后对光的防护。皮肤48h时荧光峰较低,可减少皮肤避光时间。结论:通过荧光图像早期癌诊断仪测定静脉注射HPPH在肿瘤及正常组织中的代谢,确定HPPH能作光敏诊断及光动力学治疗,注药0.3mg/kg、注药后12～24h是较佳的光敏诊断及光动力学治疗的剂量及时间。

Objective： Research on the metabolism of HPPH taking mainline on brain and tumor and skin, seek suitable dose and diagnostic and therapy time of HPPH - PDT of HPPH taking mainline. Methods： Different dose of HPPH taking mainline （0.15 ,0.3 , 0.45 mg/kg）,different time after HPPH taking mainline （before ,4.8,12.18.24.32,48 h）, we measured the fluorescence of mice g422 glioma in brain and subcutaneous axillary tumors, normal brain and skin, mucous membrane of mouth and nose. The suitable dose and diagnostic and therapy time of HPPH - PDT were got by analyzing the spectrum of fluorescence with fluorescence image diagnosis system of early cancers. Result： The fluorescence of tumors of 0.3 mg/kg and 0.45 mg/kg group was higher than that of 0.15 mg/kg group after HPPH taking mainline of mice g422 glioma; The fluorescence of tumors of 0.3 mg/kg group was approximate with 0.45 mg/kg group after HPPH taking mainline of mice g422 glioma; The time of maximum fluorescence discrepancy between tumors and normal brain and skin was 12-24 h after HPPH taking mainline of mice g422 glioma. Conclusion： The 0.3mg/kg was suitable dose and 12-24 h after taking mainline of HPPH was suitable time of HPPH-PDT of mice g422 glioma.