In vivo imaging of the mouse cholinergic projection system using [18F]FEOBV

• Published in: Alzheimer's & dementia Vol. 18; no. S6
• Main Authors: Onuska, Kate M., Shanks, Hayley R. C., Qi, Qi, Prado, Vania, Thiessen, Jonathan, Hicks, Justin, Fox, Matthew, Prado, Marco, Schmitz, Taylor W.
• Format: Journal Article
• Language: English
• Published: 01.12.2022
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.069154

Background Positron emission tomography (PET) with the [18F]‐Fluoroethoxybenzovesamicol ([18F]FEOBV) radiotracer is a promising tool for in vivo imaging of VAChT – a protein found specifically in the cholinergic system. However, the sensitivity and specificity of [18F]FEOBV uptake to known changes in VAChT protein levels remains untested. The aim of this study is therefore to use [18F]FEOBV in mouse lines where VAChT protein expression is held under precise genetic control to determine whether [18F]FEOBV brain uptake reflects the endogenous levels of VAChT present in different genetic mouse models. Method 6‐month‐old VAChT conditional forebrain knock‐out mice (VAChTNkx2.1‐Cre‐flox/flox, n = 6), VAChT hyper expressing mice (VAChTChAT‐ChR2‐eYFP, n = 6), and littermate controls (VAChT flox/flox , n = 6; C57BL/6J, n = 6), received an intravenous injection of [18F]FEOBV and were imaged dynamically on a microPET scanner for 2 and a half hours. Result When compared to controls, VAChT conditional forebrain knock‐out mice demonstrated decreased [18F]FEOBV uptake in striatal regions of the mouse brain (Figure 1, left panel). In contrast, VAChT hyper expressing mice displayed widespread increases in brain [18F]FEOBV uptake when compared to controls (Figure 1, right panel). Conclusion Together, these findings suggest that [18F]FEOBV brain uptake is a sensitive and specific measure of known changes in VAChT protein expression.