In Vivo Measurement of Vesicular Monoamine Transporter Type 2 Density in Parkinson Disease with ¹⁸F-AV-133

Abstract

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-(1)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. Voxelbased 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 Flabeled 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.

Progressive loss of striatal dopamine terminals in MPTP-induced acute parkinsonism in cynomolgus monkeys using vesicular monoamine transporter type 2 PET imaging ([18F]AV-133)

“…. This is consistent with previous studies on PD patients [23] . On day 15, no significant correlation was found between the subscores for rigidity …”

“…2). After 15 days of MPTP exposure, the SUrs of right and left side striatum of PD patients, next in the anterior putamen (−70%), and then in the caudate nucleus (−48%) [23] , which is consistent with our results. In 2010, [ 11 C]DTBZ PET imaging was used to evaluate the model of chronic MPTP-induced parkinsonism in monkeys induced by a low dose of MPTP administered over several months [33] .…”

“…Multi-tracer PET imaging in a monkey model of PD induced by chronic MPTP treatment at a low dose shows progressive nigrostriatal dopaminergic neurodegeneration, and this results in a reduced storage capacity of VMAT2 and decreased uptake of [19] , suggesting that VMAT2 binding sites are AV-133) is a novel 18 F-labeled tetrabenazine derivative that selectively binds to VMAT2 with high affi nity [20,21] . [23] .…”

Whole-Body Biodistribution and Radiation Dosimetry of 18F-FP-(+)-DTBZ (18F-AV-133): A Novel Vesicular Monoamine Transporter 2 Imaging Agent

“…These brain regions have been recognized as being related to dopamine-(nigrostriatal pathway) and serotonin (hippocampus and brain stem)-secreting neurons (35). A recent publication demonstrated the ability to differentiate healthy controls from PD subjects using 18 F-AV-133 targeting VMAT2 (20). In addition, because uptake of 18 F-AV-133 in the brain was not restricted to the nigrostriatal system, possible applications for studying the serotonin system relating to psychiatric disorders is also warranted.…”

“…An initial trial to assess the reduction of VMAT2 binding sites in patients with PD and dementia with Lewy bodies was performed by Koeppe et al (18) and Suzuki et al (19). A recent publication clearly indicated the sensitivity of 18 F-AV-133 for detecting monoaminergic terminal reductions in PD patients and concluded that 18 F-AV-133 may allow the selection of presymptomatic patients with nigrostriatal movement disorders (20).…”