Spinocerebellar ataxia 17 (SCA17) is a fatal, incurable polyglutamine (polyQ) disease, highlighting the need for effective diagnostic and therapeutic approaches. Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from lysine residues of histone and non-histone proteins, which epigenetically effect the protein synthesis. Recently, more and more evidence indicates HDAC6 inhibitor functions on aggression inhibition of alzheimer’s disease. However, no application of HDAC6 inhibitors uses in the spinocerebellar ataxia. The HDAC6 inhibitor [18F]-NC110 (i.e., [18F] 4-((5-(4-fluorobenzoyl)-1H-indol-1-yl)methyl)-N-hydroxylbenzamide) was synthesized via microwave-assisted radiofluorination from a nitro precursor, followed by the formation of a hydroxamic acid. PET/CT imaging of [18F]-NC110 and the amyloid imaging agent [18F]-Florbetaben ([18F]-FBB) in SCA17 transgenic (TG) mice demonstrated the potential of both agents for cerebellar imaging. Notably, [18F]-FBB exhibited significantly increased radioactivity in the brains of TG mice compared to wild-type (WT) mice, with higher signal accumulation in the cerebellum, indicating specificity for regions affected by SCA. These findings suggest that the expression of HDAC6 may be upregulated and highlight the potential of [18F]-FBB as a diagnostic tool for cerebellar lesions in SCAs. This study represents the first report of a HDAC6 imaging agent and the application of [18F]-FBB in SCA17 transgenic mice.