The design, synthesis and evaluation of [F]ASK1-IN-6 as the first Fuorine-18 positron emission tomography radiotracer for ASK1 neuroimaging.

Abstract

ASK1 is a key regulator in the molecular mechanisms underlying multiple neurological diseases, where it drives oxidative stress, inflammation, and apoptotic pathways. ASK1 has emerged as a potential therapeutic target in a range of neurodegenerative and neuroinflammatory diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In the study, we designed and synthesized [F]ASK1-IN-6 as the first fluorine-18 ASK1 radioligand with high purity (>95%). In in vitro autoradiography studies, [F]ASK1-IN-6 showed good binding specificity to ASK1 protein and exhibited high binding in various brain regions of mice. Furthermore, the binding specificity of the [F]ASK1-IN-6 in brain slice of wild-type mice and AD model (5 × FAD) mice were explored, the results showed [F]ASK1-IN-6 have higher binding in AD model mice, indicating that the compound has great potential for brain imaging in AD patients. Further study will focus on improving the synthesis yield of the compound and investigate its in vivo imaging in mice.