Measurement of striatal and extrastriatal dopamine transporter binding with high-resolution PET and [11C]PE2I: quantitative modeling and test-retest reproducibility.
[(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 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.
Hirvonen
Jussi
J
Department of Psychiatry, University of Turku, Turku, Finland. jueshi@utu.fi
Johansson
Jarkko
J
Teräs
Mika
M
Oikonen
Vesa
V
Lumme
Ville
V
Virsu
Pauliina
P
Roivainen
Anne
A
Någren
Kjell
K
Halldin
Christer
C
Farde
Lars
L
Hietala
Jarmo
J
D000328:Adult; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009662:Nortropanes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards*; D015203:Reproducibility of Results
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes