Measurement of striatal and extrastriatal dopamine transporter binding with high-resolution PET and [11C]PE2I: quantitative modeling and test-retest reproducibility

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Jussi HirvonenJ Hietala

Abstract

[(11)C]PE2I is a novel positron emission tomography (PET) radiotracer for the dopamine transporter (DAT). The reproducibility and reliability of [(11)C]PE2I measurements, especially in the small DAT-rich brain regions, is unknown and of critical importance to the interpretation of the data. Five healthy volunteers were scanned twice during the same day using [(11)C]PE2I and the HRRT PET scanner. Methods based on metabolite-corrected arterial plasma curve and reference region were used to estimate distribution volumes (V(T)) and binding potential (BP). Within-subject and between-subject variabilities were compared. [(11)C]PE2I accumulated in the DAT-rich striatum and the midbrain. Equilibrium of specific binding appeared late in the striatum, whereas it was reached earlier in the midbrain. Plasma metabolite analysis showed that the potentially brain-penetrant 4-hydroxymethyl metabolite represented 15% to 20% of total plasma radioactivity. V(T) and BP measurements were associated with low within-subject variability. Measurement of DAT binding in small brain regions, including the substantia nigra, is reproducible and reliable using [(11)C]PE2I and high-resolution research tomograph. A scanning time of more than 70 mins is require...Continue Reading

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