Comparison of [18F]F-CNBI and [18F]F-CNPIFE as Positron Emission Tomography Probes for Noninvasive Imaging of Glycogen Synthase Kinase-3 in Normal Mice |
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| Authors: | Heather M Stein Surendra R Gundam Aditya Bansal Nicholas R Nelson Geoffry L Curran Timothy R DeGrado Mark A Frye John D Port Val J Lowe Melissa E Murray Dr Mukesh K Pandey |
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| Institution: | 1. Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN 55905 USA;2. Department of Radiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 USA;3. Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN 55905 USA;4. Department of Radiology, Mayo Clinic, Rochester, MN 55905 USA;5. Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA |
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| Abstract: | Glycogen synthase kinase-3 α/β is involved in dysregulation of neuronal tau protein in Alzheimer's disease (AD). There is an unmet clinical need for a blood-brain barrier (BBB) permeable positron emission tomography (PET) probe for imaging of GSK-3α/β in the brain to understand the pathogenesis of AD. Herein, we synthesized two PET probes, 18F]F-CNBI and 18F]F-CNPIFE, and evaluated their BBB permeability and affinity towards GSK-3α/β. 19F]F-CNPIFE showed higher in-vitro binding towards GSK-3α/β (IC50=19.4±2.5 nM; n=3, for GSK-3α, IC50=19.4±3.8 nM; n=3, for GSK-3β) compared to 19F]F-CNBI (IC50=107.6±26.0 nM; n=4, for GSK-3α, IC50=105.3±18.2 nM; n=3, for GSK-3β). 18F]F-CNPIFE showed 9.5-fold higher brain uptake than 18F]F-CNBI, in normal FVB/NJ mice, which was increased by additional 1.5-fold on co-administration of 19F]F-CNPIFE with respect to 18F]F-CNBI. Overall, 18F]F-CNPIFE is a promising PET probe for GSK-3α/β imaging and warrants further evaluation in an AD mouse model. |
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| Keywords: | [18F]F-CNBI [18F]F-CNPIFE Glycogen synthase kinase Positron emission tomography Radiolabeling |
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