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Two of the most popular positron emission tomography (PET) tracers, [ 11 C]PE2I and [ 18 F]FE-PE2I, used to quantify dopamine transporters (DAT), display dissimilar kinetic behavior in in vivo assays. This difference can be explained by comparing values of kinetic rate constants, which characterize interaction of these tracers with DAT sites in vitro . 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 [ 18 F]FE-PE2I, seem to be better tracers in vivo , and their properties can be predicted in vitro .

In Vitro Ligand Binding Kinetics Explains the Pharmacokinetics of [18F]FE-PE2I in Dopamine Transporter PET Imaging

In Vitro Ligand Binding Kinetics Explains the Pharmacokinetics of [¹⁸F]FE-PE2I in Dopamine Transporter PET Imaging