title: Influence of O-methylated metabolite penetrating the blood-brain barrier to estimation of dopamine synthesis capacity in human L-[β-(11)C]DOPA PET.
abstract: O-methyl metabolite (L-[β-(11)C]OMD) of (11)C-labeled L-3,4-dihydroxyphenylalanine (L-[β-(11)C]DOPA) can penetrate into brain tissue through the blood-brain barrier, and can complicate the estimation of dopamine synthesis capacity by positron emission tomography (PET) study with L-[β-(11)C]DOPA. We evaluated the impact of L-[β-(11)C]OMD on the estimation of the dopamine synthesis capacity in a human L-[β-(11)C]DOPA PET study. The metabolite correction with mathematical modeling of L-[β-(11)C]OMD kinetics in a reference region without decarboxylation and further metabolism, proposed by a previous [(18)F]FDOPA PET study, were implemented to estimate radioactivity of tissue L-[β-(11)C]OMD in 10 normal volunteers. The component of L-[β-(11)C]OMD in tissue time-activity curves (TACs) in 10 regions were subtracted by the estimated radioactivity of L-[β-(11)C]OMD. To evaluate the influence of omitting blood sampling and metabolite correction, relative dopamine synthesis rate (kref) was estimated by Gjedde-Patlak analysis with reference tissue input function, as well as the net dopamine synthesis rate (Ki) by Gjedde-Patlak analysis with the arterial input function and TAC without and with metabolite correction. Overestimation of Ki was observed without metabolite correction. However, the kref and Ki with metabolite correction were significantly correlated. These data suggest that the influence of L-[β-(11)C]OMD is minimal for the estimation of kref as dopamine synthesis capacity.
authors.affiliation: 1] Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels Akita, Akita, Japan [2] Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsubara
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels Akita, Akita, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ibaraki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.affiliation: Department of Radiology and Nuclear Medicine, Research Institute for Brain and Blood Vessels Akita, Akita, Japan.
authors.forename: Toshibumi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000328:Adult; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000378:metabolism; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D004295:Dihydroxyphenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004298:Dopamine / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008745:Methylation; D049268:Positron-Emission Tomography; D011859:Radiography
chemical_list: D002247:Carbon Isotopes; D004295:Dihydroxyphenylalanine; D004298:Dopamine