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

Kimura, Yasuyuki  ,  Ichise, Masanori  ,  Ito, Hiroshi  ,  Shimada, Hitoshi  ,  Ikoma, Yoko  ,  Seki, Chie  ,  Takano, Harumasa  ,  Kitamura, Soichiro  ,  Shinotoh, Hitoshi  ,  Kawamura, Kazunori  ,  Ming-Rong, Zhang  ,  Sahara, Naruhiko  ,  Suhara, Tetsuya  ,  Higuchi, Makoto

Tau accumulation in the brain is a pathological hallmark of Alzheimer’s disease (AD) 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 considering its radiometabolite entering the brain. Methods: Seven AD and seven 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 (BPND∗ ) stably (~0.36 in high binding regions). The MRTMO BPND∗ matched the corresponding BPND∗ by the dual-input graphical model (r2 = 1.00). SUVR-1 correlated very well with MRTMO BPND∗ (r2 > 0.97). However, BPND by the single-input models did not correlate with BPND∗ by the dual-input graphical model (r2 = 0.04). Conclusions: The dual-input graphical model BPND∗ is consistent with the reference tissue BPND∗ and SUVR-1, suggesting that these parameters can accurately quantify binding of 11C-PBB3 despite the entry of its radiometabolites into the brain.KEY WORDS: PET quantification, tau, 11C-PBB3, Alzheimer’s disease

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