TY - JOUR T1 - Quantitative PET Analysis of the Dopamine D<sub>2</sub> Receptor Agonist Radioligand <sup>11</sup>C-(<em>R</em>)-2-CH<sub>3</sub>O-<em>N</em>-n-Propylnorapomorphine in the Human Brain JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 703 LP - 710 DO - 10.2967/jnumed.108.058503 VL - 50 IS - 5 AU - Tatsui Otsuka AU - Hiroshi Ito AU - Christer Halldin AU - Hidehiko Takahashi AU - Harumasa Takano AU - Ryosuke Arakawa AU - Masaki Okumura AU - Fumitoshi Kodaka AU - Michie Miyoshi AU - Mizuho Sekine AU - Chie Seki AU - Ryuji Nakao AU - Kazutoshi Suzuki AU - Sjoerd Finnema AU - Yoshio Hirayasu AU - Tetsuya Suhara AU - Lars Farde Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/5/703.abstract N2 - It has been demonstrated in vitro that the dopamine D2 receptor has 2 interconvertible affinity states for endogenous dopamine, referred to as the high- and the low-affinity states. 11C-(R)-2-CH3O-N-n-propylnorapomorphine (11C-MNPA) is a new agonist radioligand for in vivo imaging of the high-affinity state of dopamine D2 receptors using PET. In the present study, the kinetics of 11C-MNPA were examined for the first time, to our knowledge, in the human brain and analyzed using quantitative approaches with or without an arterial input function. Methods: A 90-min dynamic PET scan was obtained for 10 healthy men after an intravenous injection of 11C-MNPA. The binding potential (BPND) was calculated using the indirect kinetic method, a kinetic compartment analysis with a metabolite-corrected arterial input function. BPND was also calculated by the simplified reference tissue model (SRTM) and transient equilibrium methods, both with the cerebellum as the reference brain region. The results of the quantitative methods were compared in a cross-validation approach. Results: The highest regional radioactivity was observed in the putamen. BPND values obtained by kinetic analysis were 0.82 ± 0.09, 0.59 ± 0.11, and 0.28 ± 0.06, respectively, in the putamen, caudate, and thalamus. BPND values obtained by the SRTM and transient equilibrium methods were in good agreement with those obtained by the indirect kinetic method (r = 0.98 and r = 0.93, respectively). For all quantification methods, the BPND values based on data acquired from 0 to 60 min were in good agreement with those based on data acquired from 0 to 90 min (r = 0.90–0.99). Conclusion: The regional distribution of 11C-MNPA binding was in good agreement with previous PET studies of dopamine D2 receptors in the human brain using antagonist radioligands. The results support routine use of the SRTM and transient equilibrium methods, that is, methods that do not require an arterial input function and need a scan time of only about 60 min. 11C-MNPA should thus be useful for clinical research on the pathophysiology of neuropsychiatric disorders and estimation of dopamine D2 receptor occupancy by dopaminergic drugs. ER -