Synthesis and Pharmacological Evaluation of [11C]4-Methoxy- N-[2-(thiophen-2-yl)imidazo[1,2- a]pyridin-3-yl]benzamide as a Brain Penetrant PET Ligand Selective for the δ-Subunit-Containing γ-Aminobutyric Acid Type A Receptors

Elina T L'Estrade; Hanne D Hansen; Christina Falk-Petersen; Anne Haugaard; Nane Griem-Krey; Sascha Jung; Hartmut Lüddens; Tanja Schirmeister; Maria Erlandsson; Tomas Ohlsson; Gitte M Knudsen; Matthias M Herth; Petrine Wellendorph; Bente Frølund

doi:10.1021/acsomega.9b00434

Synthesis and Pharmacological Evaluation of [¹¹C]4-Methoxy- N-[2-(thiophen-2-yl)imidazo[1,2- a]pyridin-3-yl]benzamide as a Brain Penetrant PET Ligand Selective for the δ-Subunit-Containing γ-Aminobutyric Acid Type A Receptors

ACS Omega. 2019 May 22;4(5):8846-8851. doi: 10.1021/acsomega.9b00434. eCollection 2019 May 31.

Authors

Elina T L'Estrade^{1

2

3}, Hanne D Hansen², Christina Falk-Petersen¹, Anne Haugaard¹, Nane Griem-Krey¹, Sascha Jung⁴, Hartmut Lüddens⁵, Tanja Schirmeister⁴, Maria Erlandsson³, Tomas Ohlsson³, Gitte M Knudsen², Matthias M Herth^{1

2

6}, Petrine Wellendorph¹, Bente Frølund¹

Affiliations

¹ Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
² Neurobiology Research Unit and CIMBI, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
³ Radiation Physics, Nuclear Medicine Physics Unit, Skånes University Hospital, Barngatan 3, 222 42 Lund, Sweden.
⁴ Institute of Pharmacy & Biochemistry, Johannes Gutenberg University, D-55128 Mainz, Germany.
⁵ Department of Psychiatry and Psychotherapy, Faculty of Health and Medical Sciences, University of Medical Center, D-55131 Mainz, Germany.
⁶ Department of Clinical Physiology, Nuclear Medicine and PET, University Hospital Copenhagen, Rigshospitalet Blegdamsvej 9, 2100 Copenhagen, Denmark.

Abstract

The α_4/6βδ-containing GABA_A receptors are involved in a number of brain diseases. Despite the potential of a δ-selective imaging agent, no PET radioligand is currently available for in vivo imaging. Here, we report the characterization of DS2OMe (1) as a candidate radiotracer, ¹¹C-labeling, and subsequent evaluation of [¹¹C]DS2OMe in a domestic pig as a PET radioligand for visualization of the δ-containing GABA_A receptors.