In vivo comparison of tau radioligands ¹⁸F-THK-5351 and ¹⁸F-THK-5317

Abstract

Purpose This study compared the in vivo imaging characteristics of tau positron emission tomography (PET) ligands ¹⁸ F-THK-5351 and ¹⁸F-THK-5317 in the context of Alzheimer’s disease (AD). Additionally, reference tissue distribution volume ratio (DVR) estimation methods and standard uptake value ratio (SUVR) timing windows were evaluated to determine the optimal strategy for specific binding quantification. Methods Twenty-eight subjects (mean age 71±7yrs) underwent either dynamic 90-minute ¹⁸F-THK-5317 or ¹⁸F-THK-5351 PET scans. Bland-Altman plots were utilized to compare the simplified reference tissue method (SRTM), multilinear reference tissue method (MRTM2), and Logan reference tissue DVR estimates and to assess temporal stability of SUVR windows using cerebellar gray matter (GM) as a reference region. In vivo kinetics and DVR estimates were directly compared for 10 subjects that underwent both ¹⁸F-THK-5317 and ¹⁸F-THK-5351 PET scans. Results THK-5351 exhibited faster cerebellar GM clearance, faster cortical white matter (WM) clearance, and higher DVR estimates in AD tau-associated regions of interest (ROIs) compared to THK-5317. The MRTM2 method produced the most reliable DVR estimates for both tracers, particularly when scan duration was shortened to 60 minutes. SUVR stability was observed 50-70 minutes post injection for both tracers. Parametric images revealed differences between MRTM2, Logan and SUVR binding in WM regions for THK-5317. Conclusion THK-5317 and THK-5351 show promise for in vivo detection of AD tau. THK-5351 has more favorable pharmacokinetics and imaging characteristics compared to THK-5317.