biostudies-literatureUnknown49(4)Koike T<h4>Purpose</h4>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.<h4>Methods</h4>In vitro autoradiography (ARG) studies in the CH24H wild-type (WT) and knockout (KO) mouse brain sections were conducted using [³H]T-008. PET European journal of nuclear medicine and molecular imaging1148-1156https://www.ebi.ac.uk/biostudies/studies/S-EPMC8921165biostudies-literaturePreclinical characterization of [¹⁸F]T-008, a novel PET imaging radioligand for cholesterol 24-hydroxylase.PMC8921165Koike TKuroita TIkeda SMiyamoto MSeibyl JFowles KConstantinescu CCPapin CNishi TBarret OCole PAlagille DSunahara EMorley TTamagnan GfalsePreclinical characterization of [¹⁸F]T-008, a novel PET imaging radioligand for cholesterol 24-hydroxylase.<h4>Purpose</h4>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.<h4>Methods</h4>In vitro autoradiography (ARG) studies in the CH24H wild-type (WT) and knockout (KO) mouse brain sections were conducted using [³H]T-008. PET 2022-01-01T00:00:00Z2022 Mar2025-04-04T07:44:38.358Z2025-04-04T07:44:38.358ZS-EPMC89211653465122010.1007/s00259-021-05565-z