影响肿瘤对通过瘤内注射亚甲蓝致敏的光动力疗法反应的因素。
Factors influencing tumor response to photodynamic therapy sensitized by intratumor administration of methylene blue.
作者信息
Baran Timothy M, Giesselman Benjamin R, Hu Rui, Biel Merrill A, Foster Thomas H
机构信息
Institute of Optics, University of Rochester, Rochester, New York 14627, USA.
出版信息
Lasers Surg Med. 2010 Oct;42(8):728-35. doi: 10.1002/lsm.20962.
BACKGROUND AND OBJECTIVES
We examined tumor response to methylene blue (MB)-mediated photodynamic therapy (PDT) in a murine tumor model. The goal was to investigate the effects of drug-light interval (DLI), injection vehicle, and fluence on tumor destruction. Fluorescence and reflectance spectroscopy informed our understanding.
MATERIALS AND METHODS
EMT6 tumor cells were implanted intradermally on the backs of female BALB/c mice and grown to ∼4-mm diameter. Mice were given a 35 µl, single site, intratumor injection of 500 µg/ml MB administered in either a water or a 5% ethanol-5% Cremophor-90% saline vehicle. PDT was begun either immediately or after a 1-hour DLI with a fluence rate of 60 mW/cm(2). Each animal received a fluence of 240 or 480 J/cm(2). Fluorescence and reflectance spectra were captured before and during irradiation.
RESULTS
A protocol consisting of the Cremophor-based vehicle, 0 DLI, and a fluence of 480 J/cm(2) was the most effective, with a 55% cure rate as measured by no evidence of tumor 90 days after PDT. Use of the water vehicle with this fluence and DLI reduced the cure rate to 20%. Reducing the fluence to 240 J/cm(2) similarly reduced treatment efficacy with 0 and 1-hour DLIs. Univariate Cox proportional hazards analysis identified increased fluence, 0 versus 1-hour DLI, and the Cremophor versus water vehicle as highly significant independent predictors of long term tumor control (P < 0.01 in each case). Multivariate analysis with model selection revealed fluence and injection vehicle as the best predictors of survival hazards. Fluorescence spectroscopy in vivo showed that MB fluorescence decreased monotonically during a 2-hour dark interval but was restored by irradiation. Reflectance spectroscopy revealed that MB at this injected concentration attenuates the treatment beam significantly.
CONCLUSION
Sensitizer delivery vehicle, drug-light interval, and fluence contribute significantly to the tumor response to MB-mediated PDT.
背景与目的
我们在小鼠肿瘤模型中研究了肿瘤对亚甲蓝（MB）介导的光动力疗法（PDT）的反应。目的是研究药物 - 光照间隔（DLI）、注射载体和光通量对肿瘤破坏的影响。荧光和反射光谱为我们的理解提供了依据。
材料与方法
将EMT6肿瘤细胞皮内植入雌性BALB/c小鼠背部，待其生长至直径约4毫米。小鼠在肿瘤内单部位注射35微升500微克/毫升的MB，注射载体为水或5%乙醇 - 5%聚氧乙烯蓖麻油 - 90%生理盐水。PDT在注射后立即开始或在1小时的DLI后开始，光通量率为60毫瓦/平方厘米。每只动物接受240或480焦/平方厘米的光通量。在照射前和照射期间采集荧光和反射光谱。
结果
由基于聚氧乙烯蓖麻油的载体、0小时DLI和480焦/平方厘米的光通量组成的方案最有效，PDT后90天无肿瘤证据表明治愈率为55%。使用水载体并采用此光通量和DLI时，治愈率降至20%。将光通量降至240焦/平方厘米，在0小时和1小时DLI时同样降低了治疗效果。单变量Cox比例风险分析确定增加光通量、0小时与1小时DLI以及聚氧乙烯蓖麻油与水载体是长期肿瘤控制的高度显著独立预测因素（每种情况P < 0.01）。模型选择的多变量分析表明光通量和注射载体是生存风险的最佳预测因素。体内荧光光谱显示，在2小时的黑暗间隔期间，MB荧光单调下降，但通过照射可恢复。反射光谱显示，在此注射浓度下的MB显著衰减治疗光束。
结论
敏化剂递送载体、药物 - 光照间隔和光通量对肿瘤对MB介导的PDT的反应有显著贡献。
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