Tracking the relative in vivo pharmacokinetics of nanoparticles with PARACEST MRI.
Tracking the relative in vivo pharmacokinetics of nanoparticles with PARACEST MRI.
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DOI：
10.1021/mp900040u
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发表时间：
2009-09
影响因子：
4.9
通讯作者：
Pagel MD
中科院分区：
文献类型：
--
作者：
Ali MM;Yoo B;Pagel MD
一种追踪两种纳米颗粒体内相对药代动力学的无创检测方法可能会加速纳米颗粒生物医学应用的发展，并可能为个体患者选择个性化纳米药物提供一种方法。为了开发一种体内竞争性实验，将两种可以通过顺磁化学交换饱和转移（PARACEST）选择性检测的MRI造影剂偶联到第二代和第五代聚胺胺（PAMAM）树状聚合物上。每种试剂的CEST效应都是相对于浓度进行校准的。这些树突状PARACEST磁共振成像（MRI）造影剂的T1弛豫度的影响被发现相对于它们的CEST效应，相对于图像对比度的变化可以忽略不计，这有助于测量它们的化学交换寿命的比率。将这两种对比剂注射到小鼠乳腺癌模型中，导致两种对比剂在侧腹肿瘤中的CEST作用在时间上增加。虽然体内CEST效应不能用于确定肿瘤内每种药物的绝对浓度，但体内CEST效应的比值用于测量药物浓度的比值。该结果表明，两种纳米颗粒的相对体内药代动力学可以用PARACEST MRI进行评估。
A noninvasive assay that tracks the relative in vivo pharmacokinetics of two nanoparticles may accelerate the development of nanoparticles for biomedical applications, and may provide a method to select personalized nanomedicines for individual patients. To develop an in vivo competitive assay, two MRI contrast agents that could be selectively detected through paramagnetic chemical exchange saturation transfer (PARACEST) were conjugated to a second generation and fifth generation polyamidoamine (PAMAM) dendrimer. The CEST effects of each agent was calibrated relative to concentration. The effects of T1 relaxivities of these dendritic PARACEST magnetic resonance imaging (MRI) contrast agents were found to be negligible relative to their CEST effects with respect to changes in image contrast, which facilitated the measurement of the ratios of their chemical exchange lifetimes. Injection of both contrast agents into a mouse model of mammary carcinoma resulted in a temporal increase in the CEST effect from each agent in the flank tumor. Although the in vivo CEST effects could not be used to determine the absolute concentrations of each agent within the tumor, the ratio of the in vivo CEST effects was used to measure the ratio of the concentrations of the agents. This result demonstrated that the relative in vivo pharmacokinetics of two nanoparticles may be evaluated using PARACEST MRI.
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