HPPH光动力学治疗大鼠C6脑胶质瘤实验研究的磁共振弥散成像DWI的表现  

Evaluation of the Diffusion-Weighted Magnetic Resonance Imaging for the Growth of C6 Glioma in the Rat after the Photodynamic Therapy with 2-[1-Hexyloxyethyl]-2-Devinyl Pyropheophorbide-alpha(HPPH)

作　　者：王宇[1] 林勇[1] 沈加林[2] 张慧国[3] 赵子周[2] 刘桂勤[2] 王磊[1] 朱菁[3] 

机构地区：[1]上海交通大学医学院附属仁济医院神经外科,上海200127 [2]上海交通大学医学院附属仁济医院放射科,上海200127 [3]上海交通大学医学院附属仁济医院皮肤科,上海200127

出　　处：《应用激光》2014年第3期258-268,共11页Applied Laser

基　　金：上海市科学技术委员会动物专项资助项目(项目编号:11140900360)

摘　　要：目的：研究不同剂量新型叶绿素光敏剂HPPH光动力学疗法治疗大鼠C6脑胶质细胞移植瘤模型,无创观察磁共振波谱技术（DWI）变化、评价疗效及选择光敏剂HPPH最佳治疗剂量并与常规光敏剂血卟啉衍化物（HPD）光动力学治疗及对照组作对比。方法：建立大鼠C 6脑胶质瘤移植瘤模型,以不同剂量新型叶绿素光敏剂HPPH（0.15、0.3、0.45mg/kg）光动力学治疗,尾静脉注药后18h,以波长667nm激光照射大鼠脑肿瘤,照射功率密度200mW/cm2,照射时间20min,能量密度240J/cm2,于治疗前、治疗后7、14天（P0、P7、P14）,即肿瘤接种后第7、14、21天（T7、T14、T21天）,以磁共振平扫、增强扫描及弥散技术（DWI）无创测定肿瘤大小及ADC值。并与HPD-PDT、正常脑、对照组（未治疗、单注药、单照激光）肿瘤组的ADC值作对比。最后以病理验证。结果：ADC均值正常脑在406.01±53.59-436.25±50.23间,未治疗脑肿瘤组均值T7天、T14天、T21天分别为738±219.57、660.65±105.32、551.37±103.58,由于肿瘤长大,肿瘤细胞数的增加使弥散成像ADC值下降。各单注药、单激光对照组的变化同未治疗空白组规律相似。T检验,各未光动力学治疗对照组间比P值〉0.05无明显差异,与正常脑比P值〈0.05有显著差异。光动力学治疗组P0组与未治疗对照组相似ADC均值在609.78-705.96之间;P7天,ADC均值由于治疗后脑组织的水肿均有升高,以HPPH0.30、0.45mg/kg-PDT组均值上升较多（782.2±95.6、779.01±291.1）,其次HPPH 0.15mg/kg-PDT组（765.22±110.13）,HPD-PDT组降低一些（644.13±94.17）;P14天,ADC均值明显下降,由于肿瘤细胞光动力学治疗后的凋亡、死亡,ADC均值下降,HPPH0.30、0.45mg/kg-PDT组435.86±46.04、429.34±70.05接近正常脑值;HPPH 0.15mg/kg-PDT组稍高619.98±93.49,HPD-PDT组550.13±94.48,这两组由于肿瘤细胞的凋亡死亡较差,有较多的肿瘤细胞存在,影响弥散值,HPPH0.15mg/kg-PDT组ADC值高于HPObjective：This study is to evaluate the efficacy of the photodynamic therapy（PDT）with different doses of the photosensitizer 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha（HPPH）,by using the diffusion-weighted imaging（DWI）of magnetic resonance,on the C6 glioma in the rat,in which the optimal dose of the HPPH will be selected and the efficacy will be compared with the one of the PDT with the hematoporphyrin derivative（HPD）.Methods：In the rat C6glioma model,different doses of the HPPH（0.15,0.30,0.45mg/kg）were administrated via the veil teils of the rats.18h later,the C6 glioma was treated with a laser beam with 667nm wavelength at a laser intensity of 200m W/cm2 and an energy density of 240J/cm2 for20 min.Magnetic resonance imaging（MRI）was carried out to detect the tumor sizes and the values of the apparent diffusion coefficient（ADC）before and 7 and 14 days after the PDT（P0,P7,P14）,that is 7,14and 21days after tumor implantation（T7,T14,T21）,which was then compared with the results of the HPD-PDT in normal brains and control tumor groups including untreated,photosensitizer only,and laser light only tumor groups.The pathological examination was finally performed.Results：The ADC values varied between 406.01±53.59and 436.25±50.23in normal brain.The average ADC values of T7,T14,and T21 in untreated tumor groups were 738±219.57,660.65±105.32,and 551.37±103.58,respectively,which is significantly greater than that in the normal brain（P〈0.05）.The values were decreased with the tumor growth and the increase in tumor cell number.There was no difference in the ADC values in untreated,photosensitizer only,and laser light only tumor groups（P〉0.05）,which is similar to that of 609.78-705.96in P0 group.On P7,the values were increased due to the edema after the treatment.The ADC values in the HPPH0.15mg/kg and 0.45mg/kg-PDT groups and HPPH0.15mg/kg-PDT group were 782.2±95.6,779.01±291.1,and 765.22±110.13,respectively,while the one in HPD-PDT group was644.13±±94.17

关 键 词：大鼠C6脑胶质细胞瘤 HPPH光动力学治疗 磁共振弥散加权成像 

分 类 号：R739.41[医药卫生—肿瘤]