In vivo measurement of vesicular monoamine transporter type 2 density in Parkinson disease with 18F-AV-133

Nobuyuki Okamura, Victor L. Villemagne, John Drago, Svetlana Pejoska, Rajinder K. Dhamija, Rachel S. Mulligan, Julia R. Ellis, Uwe Ackermann, Graeme O'Keefe, Gareth Jones, Hank F. Kung, Michael J. Pontecorvo, Daniel Skovronsky, Christopher C. Rowe

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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 18F-labeled tetrabenazine derivative, 18F-(+)fluoropropyldihydrotetrabenazine (18F-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 18F-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 18F-labeled ligand 18F-AV-133 can sensitively detect monoaminergic terminal reductions in PD patients. Studies with 18F-AV-133 may allow the presymptomatic identification of individuals with disorders characterized by degeneration of dopaminergic nigrostriatal afferents.

Original languageEnglish
Pages (from-to)223-228
Number of pages6
JournalJournal of Nuclear Medicine
Volume51
Issue number2
DOIs
Publication statusPublished - 2010 Feb 1

Keywords

  • Molecular imaging
  • Neurology
  • PET
  • Parkinson disease
  • VMAT2

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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