PET Quantification of Tau Pathology in Human Brain with 11C-PBB3

Y. Kimura, M. Ichise, H. Ito, H. Shimada, Y. Ikoma, C. Seki, H. Takano, S. Kitamura, H. Shinotoh, K. Kawamura, M.-R. Zhang, N. Sahara (+2 others)
2015 Journal of Nuclear Medicine  
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 11 C-PBB3 (2-((1E,3E)-4-(6-( 11 C-methylamino)pyridin-3-yl)buta-1,3-dienyl) benzo[d]thiazol-6-ol), considering its radiometabolite entering the brain. Methods: Seven Alzheimer
more » ... ease patients and 7 healthy subjects underwent dynamic 11 C-PBB3 PET scanning. Arterial blood was sampled to obtain the parent and metabolite input functions. Quantification of 11 C-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 (MRTM O ) 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 Ã ND ) stably (∼0.36 in high-binding regions). The MRTM O BP Ã ND matched the corresponding BP Ã ND by the dual-input graphical model (r 2 5 1.00). SUVR minus 1 correlated well with MRTM O BP Ã ND (r 2 . 0.97). However, BP ND by the single-input models did not correlate with BP Ã ND by the dual-input graphical model (r 2 5 0.04). Conclusion: The dual-input graphical model BP Ã ND is consistent with the reference tissue BP Ã ND and SUVR-1, suggesting that these parameters can accurately quantify binding of 11 C-PBB3 despite the entry of its radiometabolites into the brain.
doi:10.2967/jnumed.115.160127 pmid:26182966 fatcat:n6ztkphpxrchnn7afe2rmqtmsu