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放射性标记反应的化学动力学。

Chemical Kinetics of Radiolabelling Reactions.

机构信息

University of Zurich, Department of Chemistry, Winterthurerstrasse 190, 8057, Zurich, Switzerland.

出版信息

Chemistry. 2018 Nov 7;24(62):16472-16483. doi: 10.1002/chem.201803261. Epub 2018 Aug 16.

Abstract

The application of chemical kinetics is one of the most powerful and versatile tools for investigating reaction mechanisms in complex mixtures. Kinetic studies are commonplace in traditional synthetic chemistry but are seldom used in radiopharmaceutical sciences. When deriving standard reaction rate laws, the focus is normally placed on calculating the chemical concentration of different species over time. In radiopharmaceutical synthesis, the desired product is one of the radioactive components of the mixture. Reaction conditions are optimised to obtain the radioactive product in the highest activity yield. When short-lived radionuclides are used, radioactive decay during the reaction window means that the maximum activity yield does not necessarily coincide with the chemical or decay-corrected radiochemical yields. To account for this difference in the kinetic models, it is shown how standard integrated rate laws can be modified to incorporate the contribution from radioactive decay. An example is then presented to show how radiochemical kinetics can be used to model complex systems, like [ F]FDG radiosynthesis, that involve parallel or competing reactions at the different chemical scales of the radionuclide and substrate. Increased knowledge of reaction rates, and a more wide-spread application of radiochemical kinetics, can facilitate the development of new radiolabelling reactions. Accurate identification of maximum activity yields using kinetic models also has the potential to improve the optimisation and radiochemical efficiency of all current and future radiopharmaceutical syntheses.

摘要

化学动力学的应用是研究复杂混合物反应机制最强大和最通用的工具之一。动力学研究在传统合成化学中很常见,但在放射性药物科学中很少使用。在推导标准反应速率定律时,通常重点关注随时间计算不同物种的化学浓度。在放射性药物合成中,所需的产物是混合物中放射性成分之一。优化反应条件以获得最高放射性产物活度收率。当使用短寿命放射性核素时,反应窗口期间的放射性衰变意味着最大放射性产物活度不一定与化学或衰变校正放射性化学产率一致。为了在动力学模型中考虑这种差异,展示了如何修改标准积分速率定律以纳入放射性衰变的贡献。然后,通过一个示例来说明如何使用放射性化学动力学来模拟复杂系统,例如[ F]FDG 放射性合成,其中涉及放射性核素和底物的不同化学尺度上的平行或竞争反应。对反应速率的更多了解以及更广泛地应用放射性化学动力学,可以促进新的放射性标记反应的开发。使用动力学模型准确识别最大放射性产物活度也有可能提高所有当前和未来放射性药物合成的优化和放射性化学效率。

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