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Kinetics of Nanoparticle Radiolabeling of Metalloporphyrin with 64Cu for Positron Emission Tomography (PET) Imaging
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2020-10-16 , DOI: 10.1021/acs.iecr.0c03671 Leon Z. Wang 1 , Tristan L. Lim 1 , Prashanth K. Padakanti 2 , Sean D. Carlin 2 , Abass Alavi 2 , Robert H. Mach 2 , Robert K. Prud’homme 1
Industrial & Engineering Chemistry Research ( IF 3.8 ) Pub Date : 2020-10-16 , DOI: 10.1021/acs.iecr.0c03671 Leon Z. Wang 1 , Tristan L. Lim 1 , Prashanth K. Padakanti 2 , Sean D. Carlin 2 , Abass Alavi 2 , Robert H. Mach 2 , Robert K. Prud’homme 1
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Porphyrins are a unique class of biocompatible molecules with strong light absorption and rich coordination chemistry, leading to their use as chelating agents in applications such as biomedical imaging. In particular, clusters of chelators inside a nanoparticle core can be used as contrast agents for positron emission tomography. However, the mechanism of metal chelation by porphyrins encapsulated in the hydrophobic core of a nanoparticle, an essential step in radiolabeling, has not been addressed. Here, we present a study on the kinetics of copper chelation into hematoporphyrin derivative (HpD)-encapsulated nanoparticles. Nanoparticles of 100 nm, containing HpD and sterically stabilized by a poly(ethylene glycol) block copolymer, were prepared by the kinetically controlled, rapid precipitation process Flash NanoPrecipitation. When incubated with copper ions, these HpD nanoparticles exhibit novel chelation behavior. The experimental data on UV–vis absorption and reaction modeling of the two-step chelation reaction support the formation of an intermediate complex. The reaction rates of the initial binding and the final chelation step are kon = 0.231 h–1 μM–1 and kst = 1.095 h–1, respectively. The initial binding occurs within the first 20 min and converts to the firmly chelated, metalloporphyrin. Understanding the kinetics of the binding enables the next step in advancing this technology to medical diagnostics.
中文翻译：
正电子发射断层显像（PET）的64 Cu金属卟啉纳米粒子放射性标记动力学
卟啉是一类独特的生物相容性分子，具有很强的光吸收能力和丰富的配位化学性质，因此使其在生物医学成像等应用中用作螯合剂。特别地，纳米颗粒核内的螯合剂簇可以用作正电子发射断层摄影术的造影剂。然而，尚未解决封装在纳米颗粒的疏水核中的卟啉与金属螯合的机制，这是放射性标记的必要步骤。在这里，我们介绍了铜螯合成血卟啉衍生物（HpD）封装的纳米粒子的动力学研究。通过动力学控制的快速沉淀工艺Flash NanoPrecipitation，制备了包含HpD并通过聚乙二醇嵌段共聚物进行空间稳定的100 nm纳米颗粒。当与铜离子一起孵育时，这些HpD纳米粒子表现出新的螯合行为。关于两步螯合反应的UV-vis吸收和反应建模的实验数据支持中间体配合物的形成。初始结合和最终螯合步骤的反应速率为ķ上= 0.231ħ -1 μM -1和ķ ST = 1.095ħ -1，分别。最初的结合发生在最初的20分钟内，并转化为牢固螯合的金属卟啉。了解结合的动力学使得将这项技术推进医学诊断的下一步。
更新日期：2020-10-29
中文翻译：
正电子发射断层显像（PET）的64 Cu金属卟啉纳米粒子放射性标记动力学
卟啉是一类独特的生物相容性分子，具有很强的光吸收能力和丰富的配位化学性质，因此使其在生物医学成像等应用中用作螯合剂。特别地，纳米颗粒核内的螯合剂簇可以用作正电子发射断层摄影术的造影剂。然而，尚未解决封装在纳米颗粒的疏水核中的卟啉与金属螯合的机制，这是放射性标记的必要步骤。在这里，我们介绍了铜螯合成血卟啉衍生物（HpD）封装的纳米粒子的动力学研究。通过动力学控制的快速沉淀工艺Flash NanoPrecipitation，制备了包含HpD并通过聚乙二醇嵌段共聚物进行空间稳定的100 nm纳米颗粒。当与铜离子一起孵育时，这些HpD纳米粒子表现出新的螯合行为。关于两步螯合反应的UV-vis吸收和反应建模的实验数据支持中间体配合物的形成。初始结合和最终螯合步骤的反应速率为ķ上= 0.231ħ -1 μM -1和ķ ST = 1.095ħ -1，分别。最初的结合发生在最初的20分钟内，并转化为牢固螯合的金属卟啉。了解结合的动力学使得将这项技术推进医学诊断的下一步。
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