Kukk Siim, Loog Olavi, Hiltunen Jukka-Veli, Järv Jaak
Department of Organic Chemistry, Institute of Chemistry, University of Tartu, Ravila 14a, 50411 Tartu, Estonia.
PharmaSynth AS, Teaduspargi 7, 50411 Tartu, Estonia.
ACS Med Chem Lett. 2018 Nov 29;9(12):1292-1296. doi: 10.1021/acsmedchemlett.8b00504. eCollection 2018 Dec 13.
Two of the most popular positron emission tomography (PET) tracers, [C]PE2I and [F]FE-PE2I, used to quantify dopamine transporters (DAT), display dissimilar kinetic behavior in assays. This difference can be explained by comparing values of kinetic rate constants, which characterize interaction of these tracers with DAT sites . At the same time, this kinetic analysis showed that the overall binding mechanism is similar for these two tracers and includes a fast step of complex formation followed by a slow isomerization step of this complex. Comparison with previous PE2I data revealed that isomerization of the DAT complex with PE2I occurs three times faster than in the case of FE-PE2I, which leads to the slower onset of peak specific binding of the former tracer in the DAT-rich regions. Therefore, ligands with slower isomerization on-rate, including [F]FE-PE2I, seem to be better tracers , and their properties can be predicted .
用于定量多巴胺转运体（DAT）的两种最常用的正电子发射断层扫描（PET）示踪剂，即[C]PE2I和[F]FE-PE2I，在检测中表现出不同的动力学行为。通过比较动力学速率常数的值可以解释这种差异，这些常数表征了这些示踪剂与DAT位点的相互作用。同时，这种动力学分析表明，这两种示踪剂的整体结合机制相似，包括一个快速的复合物形成步骤，随后是该复合物的缓慢异构化步骤。与先前的PE2I数据比较发现，DAT与PE2I复合物的异构化速度比与FE-PE2I复合物的异构化速度快三倍，这导致前一种示踪剂在富含DAT的区域中特异性结合峰值的出现较慢。因此，异构化速率较慢的配体，包括[F]FE-PE2I，似乎是更好的示踪剂，并且它们的性质可以被预测。
