UNLABELLED: PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain. METHODS: In this study, a novel (18)F-labeled tetrabenazine derivative, (18)F-(+)fluoropropyldihydrotetrabenazine ((18)F-AV-133), was used for the noninvasive assessment of the vesicular monoamine transporters type 2 (VMAT2) in 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) of (18)F-AV-133 was calculated using Logan graphical analysis. Voxel-based and volume-of-interest-based analyses of BP images were performed to examine brain regional reductions in VMAT2 density in PD. RESULTS: VMAT2 BP was decreased by 81% in the posterior putamen, 70% in the anterior putamen, and 48% in the caudate nucleus of PD patients. Voxel-based analysis demonstrated VMAT2 reductions in the striatum and mid brain of PD patients. Furthermore, VMAT2 BPs in the caudate nuclei significantly correlated with the clinical severity of PD. CONCLUSION: These findings indicate that the novel (18)F-labeled ligand (18)F-AV-133 can sensitively detect monoaminergic terminal reductions in PD patients. Studies with (18)F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.
UNLABELLED: PET provides a noninvasive means to evaluate the functional integrity of the presynaptic monoaminergic system in the living human brain. METHODS: In this study, a novel (18)F-labeled tetrabenazine derivative, (18)F-(+)fluoropropyldihydrotetrabenazine ((18)F-AV-133), was used for the noninvasive assessment of the vesicular monoamine transporters type 2 (VMAT2) in 17 Parkinson disease (PD) patients and 6 healthy controls. The binding potential (BP) of (18)F-AV-133 was calculated using Logan graphical analysis. Voxel-based and volume-of-interest-based analyses of BP images were performed to examine brain regional reductions in VMAT2 density in PD. RESULTS:VMAT2 BP was decreased by 81% in the posterior putamen, 70% in the anterior putamen, and 48% in the caudate nucleus of PDpatients. Voxel-based analysis demonstrated VMAT2 reductions in the striatum and mid brain of PDpatients. Furthermore, VMAT2 BPs in the caudate nuclei significantly correlated with the clinical severity of PD. CONCLUSION: These findings indicate that the novel (18)F-labeled ligand (18)F-AV-133 can sensitively detect monoaminergic terminal reductions in PDpatients. Studies with (18)F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.
Authors: Noble George; Emily G Gean; Ayon Nandi; Boris Frolov; Eram Zaidi; Ho Lee; James R Brašić; Dean F Wong Journal: CNS Drugs Date: 2015-04 Impact factor: 5.749
Authors: Nian Xiong; Nuomin Li; Eden Martin; Jinlong Yu; Jie Li; Jing Liu; David Yue-Wei Lee; Ole Isacson; Jeffery Vance; Hong Qing; Tao Wang; Zhicheng Lin Journal: Neurotherapeutics Date: 2016-07 Impact factor: 7.620