PET quantification of tau pathology in human brain with 11C-PBB3

Abstract

Tau accumulation in the brain is a pathologic hallmark of Alzheimer disease and other tauopathies. Quantitative visualization of tau pathology in humans can be a powerful method as a diagnostic aid and for monitoring potential therapeutic interventions. We established methods of PET quantification of tau pathology with 11C-PBB3 (2-((1E,3E)-4-(6-(11C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. Methods: Seven Alzheimer disease patients and 7 healthy subjects underwent dynamic 11C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of 11C-PBB3 binding was performed using dual-input models that take the brain metabolite activity into consideration, traditional single-input models without such considerations, and the reference tissue model (MRTMO) and standardized uptake value ratio (SUVR). The cerebellar cortex was used as the reference tissue for all methods. Results: The dual-input graphical models estimated binding parameter (BP∗ND) stably (∼0.36 in high-binding regions). The MRTMO BP∗ND matched the corresponding BP∗ND by the dual-input graphical model (r2 5 1.00). SUVR minus 1 correlated well with MRTMO BP∗ND (r2. 0.97). However, BPND by the single-input models did not correlate with BP∗ND by the dual-input graphical model (r2 5 0.04). Conclusion: The dual-input graphical model BP∗ND is consistent with the reference tissue BP∗ND and SUVR-1, suggesting that these parameters can accurately quantify binding of 11C-PBB3 despite the entry of its radiometabolites into the brain.