Quantitative evaluation of tau PET tracers ¹⁸F-THK5351 and ¹⁸F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization.

Abstract

Off-target binding in the reference region is a challenge for recent tau tracers ¹⁸F-AV-1451 and ¹⁸F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of the SUVR, and improve the quantitative assessment of tau deposition. The SUVP normalizes uptake values by their mode and standard deviation. Instead of using a reference region, the SUVP derives the contrast from unaffected voxels over the whole brain. Using SUVP and SUVR methods, we evaluated the global and regional tau binding of ¹⁸F-THK5351 and ¹⁸F-AV-1451 on two independent cohorts (N = 18 and 32, respectively), each with cognitively normal (NL) subjects and Alzheimer's disease (AD) subjects. Both tracers showed significantly increased binding for AD in the targeted cortical areas. In the temporal cortex, SUVP had a higher classification success rate (CSR) than SUVR (0.96 vs 0.89 for ¹⁸F-THK5351; 0.86 vs 0.75 for ¹⁸F-AV-1451), as well as higher specificity under fixed sensitivity around 0.80 (0.70 vs 0.45 specificity for ¹⁸F-THK5351; 1.00 vs 0.78 for ¹⁸F-AV-1451). In the cerebellar cortex, an AD-NL group difference with effect size (Cohen's d) of 0.62 was observed for AV-1451, confirming the limitation of the SUVR approach using this region as a reference. A smaller cerebellar effect size (0.09) was observed for THK5351. The SUVP method reduces the bias of the reference region and improves the NL-AD classification compared to the SUVR approach.