Quantification of dopamine transporter in human brain using positron emission tomography with 18F-FE-PE2I

18F-FE-PE2I, 18F-(E)-N-(3-iodoprop-2E-enyl)-2beta-carbofluoroethoxy-3beta-(4-methylphenyl)nortropane, is a new PET radioligand with a high affinity and selectivity for the dopamine transporter (DAT) . In non-human primates, 18F-FE-PE2I showed a faster kinetics and less production of potentially BBB-permeable radiometabolite as compared with 11C-PE2I. The aims of this study were to examine the quantification of DAT using 18F-FE-PE2I and to assess the effect of radiometabolites of 18F-FE-PE2I on the quantification in healthy humans. Methods: A 90-min dynamic PET scan was performed on 10 healthy men after intravenous injection of 18F-FE-PE2I. Kinetic compartment model analysis with a metabolite-corrected arterial input function was carried out. The effect of radiometabolites on the quantification was evaluated by time-stability analyses. The simplified reference tissue model (SRTM) method with the cerebellum as a reference region was evaluated as a non-invasive method of quantification. Results: After the injection of 18F-FE-PE2I, the whole brain radioactivity showed a high peak (~3-5 SUV) and fast washout. The radioactive uptake of 18F-FE-PE2I in the brain was according to the relative density of the DAT (striatum>midbrain>thalamus). The cerebellum showed the lowest uptake. Tissue time-activity curves were well described by the 2-tissue compartment model (TCM) as compared with the 1-TCM for all subjects in all regions. Time stability analysis showed stable estimation of VT with 60-min or longer scan durations, indicating the small effect of radiometabolites. Binding potentials in the striatum and midbrain were well estimated by the SRTM method with modest inter-subject variability. Although SRTM yielded a slight underestimation and overestimation in regions with high and low DAT densities, respectively, binding potentials by the SRTM method were well correlated to the estimates by the indirect kinetic method with 2-TCM. Conclusion: 18F-FE-PE2I is a promising PET radioligand for quantifying DAT. The binding potentials could be reliably estimated in both the striatum and midbrain using both the indirect kinetic and SRTM method with scan duration of 60 min. Although radiometabolites of 18F-FE-PE2I in plasma possibly introduced some effects on the radioactivity in the brain, the effects on estimated binding potential were likely to be small