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Quantifying receptor density in vivo using a dual-probe approach withfluorescence molecular imaging

机译:使用双重探针方法定量体内的受体密度使用双探针分子成像

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Molecular imaging technologies are advancing rapidly and optical techniques in particular are set to play a large role in preclinical pharmaceutical testing. These approaches, however, are generally unable to quantify the level of expression of imaging probe reporters. In this study a novel method of quantification is presented using dual-probe fluorescence imaging, where an endothelial growth factor receptor (EGFR) fluorescent probe was paired with a non-targeted probe before being injected, and tracer kinetic compartmental modeling was used to determine EGFR expression in a region of interest from the uptake curves of the two drugs in that region. The approach was tested out in a simulation experiment and then applied in an in vivo study in one mouse to investigate EGFR expression in various tissue types (pancreas, pancreas tumor, and leg). The binding potentials (a unitless correlate of target availability) of EGFR expression in the various tissue types were 8.57, 25.64, and 0.11 for the pancreas, pancreas tumor, respectively. For the pancreas and leg, these results correlate well with expected levels of EGFR expression, with the pancreas demonstrating a much higher expression than the skin and also as expected, the tumor expressed much more EGFR than either healthy tissue.
机译:分子成像技术正在迅速推进,特别是光学技术被设定为在临床前药物测试中发挥大作用。然而,这些方法通常无法量化成像探针记者的表达水平。在该研究中,使用双探针荧光成像来呈现一种新的定量方法,其中内皮生长因子受体(EGFR)荧光探针在注射之前与非靶向探针配对,并且使用示踪动力学室内建模来确定EGFR来自该地区两种药物的吸收曲线的感兴趣区域的表达。该方法在模拟实验中进行了测试,然后在一只小鼠中施用在体内研究中,以研究各种组织类型(胰腺,胰腺肿瘤和腿部)的EGFR表达。对于胰腺,胰腺胰腺肿瘤的抗富尔表达的结合电位(目标可用性的无单位相关性)分别为8.57,25.64和0.11。对于胰腺和腿部,这些结果与预期的EGFR表达水平相关,胰腺表现出比皮肤更高的表达,并且也如预期的那样,肿瘤表达比健康组织更多的EGFR。

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