Progressive Supranuclear Palsy: In Vivo SPECT Imaging of Presynaptic Vesicular Acetylcholine Transporter with [123I]-Iodobenzovesamicol

Abstract

To evaluate the integrity of brain cholinergic pathways in vivo in patients with progressive supranuclear palsy (PSP) by measuring the vesicular acetylcholine transporter expression at single photon emission computed tomography (SPECT) with [123I]-iodobenzovesamicol. All participants provided informed written consent according to institutional human ethics committee guidelines. Ten patients with PSP and 12 healthy volunteers underwent dynamic [123I]-iodobenzovesamicol SPECT and magnetic resonance (MR) imaging. CT and MR images were used to register the dynamic SPECT image to the Montreal Neurologic Institute brain template, which includes the regions of interest of the striatum and the septo-hippocampal, innominato-cortical, and ponto-thalamic cholinergic pathways. For each region of interest, pharmacokinetic modeling of regional time activity curves was used to calculate [123I]-iodobenzovesamicol to vesicular acetylcholine transporter binding potential value, proportional to vesicular acetylcholine transporter expression. When compared with control participants, patients with PSP had binding potential values that were unchanged in the striatum and septohippocampal pathway, significantly lower in the anterior cingulate cortex (P=.017) in the innominatocortical pathway, and significantly decreased in the thalamus (P=.014) in the pontothalamic cholinergic pathway. In addition, binding potential values in the thalamus were positively correlated with those in the pedunculopontine nucleus (ρ=0.81, P<.004) and binding potential values in both the thalamus (ρ=-0.88, P<.001) and pedunculopontine nucleus (ρ=-0.80, P<.010) were inversely correlated with disease duration. Cholinergic pathways were differentially affected in the PSP group, with a significant alteration of pontothalamic pathways that increased with disease progression at both cell body and terminal levels, while the innominatocortical pathway was only mildly affected, and the septohippocampal pathway and the striatum were both preserved.