Truncation of blood curves to enhance imaging and therapy with monoclonal antibodies.
Truncation of blood curves to enhance imaging and therapy with monoclonal antibodies.
复制标题
截断血液曲线以增强单克隆抗体的成像和治疗。
DOI：
10.1118/1.598963
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发表时间：
2000
期刊：
影响因子：
3.8
通讯作者：
Wong,JY
中科院分区：
文献类型：
--
作者：
Williams,LE;Liu,A;Wu,AM;Yazaki,PJ;Yamauchi,DM;Lopatin,G;Raubitschek,AA;Wong,JY
单克隆抗体（Mab）靶向实体瘤部位是活性与时间的血液曲线的函数。已经建议将血液曲线人为地减小到接近零，使得肿瘤和血液摄取之间的对比度最大化。我们分析了肿瘤吸收作为血液曲线截断时间的函数。通过使用卷积方法，我们能够找到在诊断或治疗动物示例中将血液曲线设置为零的最佳时间。使用来自涉及LS 174T结肠直肠肿瘤模型的裸鼠研究的先前数据，考虑了两种碘化抗CEA工程化片段，双抗体和微抗体。使用品质因数（FOM）比较普通和截断的血液曲线及其相关的肿瘤蓄积。使用标签，可以看出，当测量的肿瘤摄取达到最大值时，诊断截断的适当时间发生。治疗的对应点（作为标签）是在无限时间。我们还表明，使用传统的索引导致的模糊性，在截断时间的选择。传统的治疗指标，即肿瘤吸收积分与血液吸收积分之比，被发现是一个独立于的数值常数，该比值被证明是肿瘤脉冲响应函数的积分。使用这种卷积技术来评估灌注材料的截断可能也适用于多步过程以及其他肿瘤特异性药物的病变靶向。
Targeting of monoclonal antibody (Mab) to solid tumor sites is a function of the blood curve of activity versus time. It has been suggested that the blood curve be artificially reduced to approach zero so that the contrast between tumor and blood uptake is maximized. We analyzed tumor uptake as a function of the time of blood curve truncation. By using a convolution approach, we were able to find the optimal times for setting the blood curve to zero in either diagnostic or therapeutic animal examples. Two iodinated anti‐CEA engineered fragments, diabody and minibody, were considered using previous data from nude mouse studies involving the LS174T colorectal tumor model. Figures of merit (FOMs) were used to compare ordinary and truncated blood curves and their associated tumor accumulations. Using a label, it was seen that the appropriate time for diagnostic truncation occurred when tumor uptake, as measured, was a maximum. The corresponding point for therapy (with as a label) was at infinite time. We also demonstrated that the use of traditional indices led to ambiguities in the choice of truncation times. The traditional therapy index, the ratio of the integral of the tumor uptake to the integral of the blood uptake, was found to be a numerical constant independent of This ratio was proved to be the integral of the tumor impulse response function. Use of such convolution techniques to assess truncation of the perfused material is probably also applicable to multistep processes as well as to lesion targeting with other tumor‐specific pharmaceuticals.