Synthesis and Pharmacokinetic Study of a 11C-Labeled Cholesterol 24-Hydroxylase Inhibitor Using ‘In-Loop’ [11C]CO2 Fixation Method

Cholesterol 24-hydroxylase is a monooxygenase encoded by CYP46A1, which is specifically expressed in the brain where it controls cholesterol elimination by producing 24S-hydroxylcholesterol (24-HC) as the major metabolite. Selective blockade of CYP46A1 activity may suppress neuronal cell death, Aβ deposition and p-tau accumulation by decreasing 24-HC formation, which thereafter serves as potential therapeutic pathway for Alzheimer’s disease. In this work, we showcase the efficient synthesis and preliminary pharmacokinetic evaluation of a novel cholesterol 24-hydroxylase inhibitor 1 by positron emission tomography study.