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

¹ Department of Nuclear Medicine and Centre for PET, Austin Health, Melbourne, Victoria, Australia; ² Mental Health Research Institute, University of Melbourne, Melbourne, Victoria, Australia; ³ Howard Florey Institute, University of Melbourne, and Centre for Neuroscience, University of Melbourne, Melbourne, Victoria, Australia; ⁴ Department of Neurology, Austin Health, Melbourne, Victoria, Australia; ⁵ Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania; and ⁶ Avid Radiopharmaceuticals Inc., Research and Development, Philadelphia, Pennsylvania

Correspondence: For correspondence or reprints contact: Christopher C. Rowe, Department of Nuclear Medicine, Centre for PET, Austin Health, 145 Studley Rd., Heidelberg, VIC 3084, Australia. E-mail: Christopher.Rowe{at}austin.org.au

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.

Key Words: molecular imaging • neurology • PET • Parkinson disease • VMAT2 • PET

COPYRIGHT © 2010 by the Society of Nuclear Medicine, Inc.

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