Quantitative PET Analysis of the Dopamine D2 Receptor Agonist Radioligand 11C-(R)-2-CH3O-N-n-Propylnorapomorphine in the Human Brain

Journal of Nuclear Medicine

Tatsui Otsuka¹  Hidehiko Takahashi¹  Michie Miyoshi¹  Tetsuya Suhara¹  Kazutoshi Suzuki¹  Mizuho Sekine¹  Ryosuke Arakawa¹  Ryuji Nakao¹  Yoshio Hirayasu¹  Masaki Okumura¹  Harumasa Takano¹  Hiroshi Ito¹  Sjoerd Finnema¹  Christer Halldin¹  Chie Seki¹  Fumitoshi Kodaka¹  Lars Farde¹ 

关键词: ¹¹C-MNPA;    agonist;    dopamine D₂ receptor;    positron emission tomography;    human;   

DOI  :  10.2967/jnumed.108.058503

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown