Radiosynthesis and evaluation of a novel 18F-labeled tracer for PET imaging of glycogen synthase kinase 3

Zhiwei Xiao; Yinlong Li; Ahmed Haider; Stefanie K Pfister; Jian Rong; Jiahui Chen; Chunyu Zhao; Xin Zhou; Zhendong Song; Yabiao Gao; Jimmy S Patel; Thomas L Collier; Chongzhao Ran; Chuangyan Zhai; Hongjie Yuan; Steven H Liang

doi:10.62347/OBZS8887

Radiosynthesis and evaluation of a novel ¹⁸F-labeled tracer for PET imaging of glycogen synthase kinase 3

Am J Nucl Med Mol Imaging. 2024 Oct 15;14(5):327-336. doi: 10.62347/OBZS8887. eCollection 2024.

Authors

Zhiwei Xiao^{1

2}, Yinlong Li^{1

2}, Ahmed Haider^{1

2}, Stefanie K Pfister², Jian Rong^{1

2}, Jiahui Chen^{1

2}, Chunyu Zhao^{1

2}, Xin Zhou¹, Zhendong Song¹, Yabiao Gao¹, Jimmy S Patel^{1

3}, Thomas L Collier^{1

2}, Chongzhao Ran⁴, Chuangyan Zhai¹, Hongjie Yuan⁵, Steven H Liang^{1

2}

Affiliations

¹ Department of Radiology and Imaging Sciences, Emory University Atlanta, GA 30322, USA.
² Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital and Department of Radiology, Harvard Medical School Boston, MA 02114, USA.
³ Department of Radiation Oncology, Winship Cancer Institute of Emory University Atlanta, GA 30322, USA.
⁴ Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School Boston, MA 02114, USA.
⁵ Department of Pharmacology and Chemical Biology, Emory University School of Medicine Atlanta, GA 30322, USA.

Abstract

Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine kinase family that regulates diverse biological processes including glucose metabolism, insulin activity and energy homeostasis. Dysregulation of GSK3 is implicated in the development of several diseases such as type 2 diabetes mellitus, Alzheimer's disease (AD), and various cancer types. In this study, we report the synthesis and evaluation of a novel positron emission tomography (PET) ligand compound 28 (codenamed [¹⁸F]GSK3-2209). The PET ligand [¹⁸F]28 was obtained via copper-mediated radiofluorination in more than 32% radiochemical yields, with high radiochemical purity and high molar activity. In vitro autoradiography studies in rodents demonstrated that this tracer exhibited a high specific binding to GSK3. Furthermore, PET imaging studies of [¹⁸F]28 revealed its ability to penetrate the blood-brain barrier (BBB).

Keywords: 18F-labeled; Alzheimer’s disease; Glycogen synthase kinase 3; PET; radiotracer.