1. ¹Department of Psychiatry, University of Turku, Turku, Finland
2. ²Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland
3. ³Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Correspondence: Dr J Hirvonen, Turku PET Centre, Kiinamyllynkatu 4-8, Turku, FIN-20520, Finland. E-mail: jueshi@utu.fi

Received 28 August 2007; Revised 4 December 2007; Accepted 4 December 2007; Published online 9 January 2008.

Abstract

[ ¹¹C] PE2I is a novel positron emission tomography (PET) radiotracer for the dopamine transporter (DAT). The reproducibility and reliability of [ ¹¹C] 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 [ ¹¹C] 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. [ ¹¹C] 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 [ ¹¹C] PE2I and high-resolution research tomograph. A scanning time of more than 70 mins is required for the striatum, while less is sufficient for DAT quantification in the midbrain. The previously suggested involvement of the potentially brain-penetrant radioactive metabolite in the quantification should be further studied.