Preclinical characterization of [¹⁸F]T-008, a novel PET imaging radioligand for cholesterol 24-hydroxylase.

ABSTRACT:

Purpose

Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that plays a major role in brain cholesterol homeostasis by converting cholesterol into 24S-hydroxycholesterol. The selective CH24H inhibitor soticlestat (TAK-935) is being pursued as a drug for treatment of seizures in developmental and epileptic encephalopathies. Herein, we describe the successful discovery and the preclinical validation of the novel radiolabeled CH24H ligand (3-[¹⁸F]fluoroazetidin-1-yl){1-[4-(4-fluorophenyl)pyrimidin-5-yl]piperidin-4-yl}methanone ([¹⁸F]T-008) and its tritiated analog, [³H]T-008.

Methods

In vitro autoradiography (ARG) studies in the CH24H wild-type (WT) and knockout (KO) mouse brain sections were conducted using [³H]T-008. PET

SUBMITTER: Koike T 

PROVIDER: S-EPMC8921165 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature