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

The present study explores the noninvasive positron emission tomography (PET) imaging for the detection of GSK-3β overexpression using [(18)F]F-CNPI and [(18)F]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. [(18)F]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 [(18)F]F-CNBI was lower in all the groups compared to that of [(18)F]F-CNPI. The late-stage GSK-3β transgenic mice having higher GSK-3β expression showed higher uptake of [(18)F]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.