The design, synthesis and evaluation of the first carbon-11 positron emission tomography radiotracer for ASK1 imaging.
The design, synthesis and evaluation of the first carbon-11 positron emission tomography radiotracer for ASK1 imaging.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Charlestown, US · Author affiliation
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.Location evidence
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Original abstract
Apoptosis signal regulating kinase 1 (ASK1) plays a central role in the molecular pathogenesis of various neurological disorders by mediating inflammation, oxidative stress, and apoptosis. ASK1 has emerged as an important therapeutic target in a range of neurodegenerative and neuroinflammatory disorders, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Herein, we describe the development and preclinical evaluation of [11C]HYF038 as the first positron emission tomography radiotracer for imaging ASK1. In vitro autoradiography, [11C]HYF038 performed good specific binding to the ASK1 proteins in the mice brain regions, data are expressed as the density light units per square millimeter (DLU/mm2) in the blocking group was reduced by 28%. In vivo PET imaging of [11C]HYF038 in rodent model demonstrated a certain blood-brain barrier (BBB) penetration with SUV = 0.5, the biodistribution result of [11C]HYF038 in different organs showed that [11C]HYF038 is mainly metabolized in the liver. These findings indicate that [11C]HYF038 can act as a promising lead for the further development of PET tracers to image ASK1 in neurodegenerative disease progression.