Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with ¹⁸F-FEOBV

Objectives: To quantify brain cholinergic denervation in patients with dementia with Lewy bodies (DLB) using PET imaging with the vesicular acetylcholine transporter (VAChT) ¹⁸F-fluoroethoxybenzovesamicol (¹⁸F-FEOBV) radioligand. We investigated the feasibility of using supratentorial white matter as a reference region for non-invasive assessment of cortical and subcortical VAChT binding in DLB patients using a delayed 3-3.5 hr imaging protocol.

Methods: Four DLB patients DLB; 2 females; mean age 76.0±1.4 years, duration of disease 4.2±2.2 years and Mini-Mental State Exam score of 17.8±5.1) and normal age- and gender-matched elderly control subjects (NCs) underwent delayed brain PET imaging 3-3.5 hours (scanned every 5 minutes for a total of 6 frames) following the intra-venous injection of 8 mCi of ¹⁸F-FEOBV. Delayed imaging distribution volume ratios (DVR) were calculated using supratentorial white matter as reference region. RESULTS: Average time activity curve activity in the segmented white matter between the DLB patients and NCs were within 1% of each other. Significant lower cortical and subcortical gray matter target curves were seen in the DLB compared to the NCs (Figure). Diffuse cortical VAChT losses (frontal -16.8%, t =-6.2, P<0.0001; temporal -26.2%, t =-7.6, P<0.0001; parietal -20.1%, t =-6.7, P<0.0001 and occipital cortex -16.8%, t =-6.26 P<0.0001) were present in the DLB subjects compared to the NCs. We also observed significant VAChT reductions in the DLB subjects in the hippocampus (-18.8%, t =-6.6, P<0.0001), thalamus (-21.0%, t =-2.8, P=0.01), cerebellar vermis (-7.2%, t_estimated=-2.2, P=0.04), and amygdala (-17.2%, t =-6.4, P<0.0001); however, not in the caudate nucleus (-13.6%, t=-2.2, p=0.21) or putamen (-7.4%, t_estimated=-2.2, P=0.42). CONCLUSIONS: These data show widespread cortical and subcortical VAChT reductions in DLB patients compared to the normal control elderly subjects. The nearly identical supratentorial white matter time activity curves between DLB patients and NCs support the feasibility of using the white matter as a non-invasive reference region to quantify cortical and subcortical gray matter VAChT uptake.

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