2. Academic Validation
  3. Evaluation of [18F]F-CNBI and [18F]F-CNPI PET Probes in GSK-3β Transgenic Mice

Evaluation of [18F]F-CNBI and [18F]F-CNPI PET Probes in GSK-3β Transgenic Mice

  • ACS Chem Neurosci. 2025 Sep 3;16(17):3340-3353. doi: 10.1021/acschemneuro.5c00442.
Manasa Kethamreddy 1,  Surendra Reddy Gundam 1,  Andy Gonzalez Rivera 1,  Aditya Bansal 1,  Do Young Lim 2,  Sharmila Giri 3,  Nicholas B Larson 3,  Bharath Wootla 4,  Val J Lowe 1,  Darren J Baker 2 5 6 7,  Mukesh K Pandey 1 8 9
Affiliations

Affiliations

  • 1 Division of Nuclear Medicine,Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 2 Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 3 Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 4 Mayo Clinic Research Innovation, Rochester, Minnesota 55905, United States.
  • 5 Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 6 Robert and Arlene Kogod Center on Aging Rochester, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 7 Paul F. Glenn Center for Biology of Aging Research, Mayo Clinic, Rochester, Minnesota 55905, United States.
  • 8 Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota 55905, United States.
  • 9 Department of Pharmacology, Mayo Clinic, Rochester, Minnesota 55905, United States.
PMID: 40815164 DOI: 10.1021/acschemneuro.5c00442
Abstract

The present study explores the noninvasive positron emission tomography (PET) imaging for the detection of GSK-3β overexpression using [18F]F-CNPI and [18F]F-CNBI in a GSK-3β overexpressing transgenic mouse model. Herein, we validated GSK-3β overexpression in different brain regions by genotyping and Western blot. PET scans and ex vivo biodistribution were performed in normal mice and early stage and late-stage GSK-3β transgenic mice with and without the P-gp inhibitor, Tariquidar. Both probes are found in the substrate of the P-gp transporter. [18F]F-CNPI showed significantly higher brain uptake in normal and GSK-3β overexpressing mice with the P-gp inhibitor compared to those without the P-gp inhibitor. The uptake of [18F]F-CNBI was lower in all the groups compared to that of [18F]F-CNPI. The late-stage GSK-3β transgenic mice having higher GSK-3β expression showed higher uptake of [18F]F-CNPI in the brain as compared to normal and early stage GSK-3β transgenic mice brains. To the best of our knowledge, this is the first report evaluating any GSK-3 PET probe in a GSK-3β overexpressing transgenic mouse model. The developed GSK-3β overexpressing transgenic mouse model can be efficiently employed to evaluate an array of GSK-3 PET probes.

Keywords

Alzheimer’s disease; P-glycoprotein; P-glycoprotein inhibitor; Tariquidar; [18F]F-CNBI; [18F]F-CNPI; dementia; fluorine-18; glycogen synthase kinase-3β; positron emission tomography; transgenic mouse model.

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