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yuanyisuo金虫 (小有名气)
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[求助]
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In vivo bioluminescence imaging is a powerful tool for assessing tumor burden and quantifying therapeutic response in xenograft models. However, this technique exhibits significant variability as a consequence of differences in substrate administration, as well as the tumor size, type, and location. Here, we present a novel pharmacokinetic (PK) approach that utilizes bioluminescence image data. The sample data are taken from mice implanted with a melanoma tumor cell line that was transfected to express the firefly (Photinus pyralis) luciferase gene. At 5, 7, and 10 days postimplant, intraperitoneal injections of D-luciferin were given to monitor the uptake into the tumor, and the tumor volume was measured using ultrasound. A multicompartment PK model was used to simultaneously fit all experiments for each mouse.Weobserved that the rates of luciferin transport in and out of the tumor exhibited a clear dependence on the tumor volume. Also, the rate of tumor influx increased faster than did the efflux, resulting in a shortening of the time to peak-luciferin concentration as the tumor grows. The time of the peak concentration correlated poorly with the tumor volume, but the peak bioluminescence signal and the area under the curve both exhibited a dependence on the tumor surface area. These results agree with Starling's hypothesis relating the higher interstitial fluid pressure in the tumor with flux across the boundary, and suggest that drug transport may depend more strongly on the surface area of the tumor than its volume. These observations provide a quantitative physical rationale for molecular targeting of therapeutics that enhance trapping and overcome the accelerated efflux kinetics. |
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fjtony163
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2楼2011-10-21 16:26:52
yuanyisuo
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3楼2011-10-21 18:00:32
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yuanyisuo(金币+70, 翻译EPI+1): 多谢 2011-10-23 20:50:46
爱与雨下(金币+2): 2011-10-24 08:37:22
yuanyisuo(金币+70, 翻译EPI+1): 多谢 2011-10-23 20:50:46
爱与雨下(金币+2): 2011-10-24 08:37:22
| 在生物活体中，对于评估肿瘤负担以及量化在异种移植模式下的理疗反应，生物发光成像是一项强有力的工具。然而，这一技术随着基体管理、肿瘤尺寸、类型和位置的不同会产生显著的变化。在这里，我们呈现了一种采用生物发光成像数据的新型药代动力学方法。样本数据来自于带有一种被移植有黑素瘤细胞株的老鼠，而该细胞株的转移用来表达萤火虫的荧光素酶基因。在植入后的第五、七和第十天，对其注射D-荧光素酶，用以显示肿瘤的摄取量，而且通过超声来测量肿瘤的体积。为了对每一个老鼠同时进行试验，我们采用了一个带有多隔室的药代动力学模式。我们观察到荧光素酶输入肿瘤和输出肿瘤的速率明显依赖于肿瘤的体积。而且，其输入肿瘤的速率要快于输出的速率，这导致了随着肿瘤的不断生长荧光素酶达到峰值浓度的时间的缩短。尽管峰值浓度的时间与肿瘤的体积相关性很差，但是峰值的生物发光信号和在峰值浓度曲线下的面积却依赖于肿瘤的表面积。这些结果与斯塔林假设：在肿瘤内的组织液压力越大，其沿着界面的流量就愈大想吻合，从而说明药物的转移（运输）或许更强烈地依赖于肿瘤的表面积而非其体积。这些观察结果为治疗学的分子靶向提供了一个数学上的物理基本原理，从而有利于阻止和克服加速的流出动力学。 |
4楼2011-10-23 20:19:05
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