Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy

Area of Science:

• Neuroimaging
• Neurology
• Molecular Imaging

Background:

• ¹⁸F-9-fluoropropyldihydrotetrabenazine (¹⁸F-FP-DTBZ) positron emission tomography (PET) is a validated biomarker for Parkinson's disease (PD).
• Evidence for its utility in progressive supranuclear palsy (PSP) is limited.
• Vesicular monoamine transporter 2 (VMAT2) is the target of ¹⁸F-FP-DTBZ.

Purpose of the Study:

• To evaluate striatal and extrastriatal monoaminergic disruption in PSP using ¹⁸F-FP-DTBZ PET.
• To compare VMAT2 binding patterns between PSP, PD, and healthy controls (HCs).
• To correlate VMAT2 binding with clinical characteristics in PSP patients.

Main Methods:

• ¹⁸F-FP-DTBZ PET/CT scans were performed on 58 PSP patients, 23 PD patients, and 17 HCs.
• Images were spatially normalized and analyzed using a region-of-interest approach.
• VMAT2 binding was assessed in striatal and extrastriatal regions.

Main Results:

• Significant differences in VMAT2 binding were observed in the striatum and substantia nigra across groups (P < 0.001).
• PSP patients showed more severe caudate VMAT2 disruption than PD patients (P < 0.001).
• Striatal VMAT2 binding correlated with postural instability, and hippocampal binding correlated with cognitive scores in PSP patients.

Conclusions:

• ¹⁸F-FP-DTBZ PET highlights significant caudate VMAT2 binding differences between PSP, PD, and HCs.
• VMAT2 binding in the striatum and hippocampus reflects the severity of postural instability and cognitive impairment, respectively, in PSP.