Authors: Ahmed Haider, Chunyu Zhao, Lu Wang, Zhiwei Xiao, Jian Rong, Xiaotian Xia, Zhen Chen, Stefanie K. Pfister, Natalia Mast, Eylan Yutuc, Jiahui Chen, Yinlong Li, Tuo Shao, Geoffrey I. Warnock, Alyaa Dawoud, Theresa R. Connors, Derek H. Oakley, Huiyi Wei, Jinghao Wang, Zhihua Zheng, Hao Xu, April T. Davenport, James B. Daunais, Richard S. Van, Yihan Shao, Yuqin Wang, Ming-Rong Zhang, Catherine Gebhard, Irina Pikuleva, Allan I. Levey, William J. Griffiths, Steven H. Liang
Published: 2022-10-05
DOI: 10.1126/scitranslmed.adc9967
Source: Full article
Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies. Here, we describe the development and testing of a CYP46A1-targeted positron emission tomography (PET) tracer,