UNLABELLED: 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 disease 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 (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 ([Formula: see text]) stably (∼0.36 in high-binding regions). The MRTMO [Formula: see text] matched the corresponding [Formula: see text] by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO [Formula: see text] (r(2) > 0.97). However, BPND by the single-input models did not correlate with [Formula: see text] by the dual-input graphical model (r(2) = 0.04). CONCLUSION: The dual-input graphical model [Formula: see text] is consistent with the reference tissue [Formula: see text] and SUVR-1, suggesting that these parameters can accurately quantify binding of (11)C-PBB3 despite the entry of its radiometabolites into the brain.
UNLABELLED: 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 diseasepatients 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 (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 ([Formula: see text]) stably (∼0.36 in high-binding regions). The MRTMO [Formula: see text] matched the corresponding [Formula: see text] by the dual-input graphical model (r(2) = 1.00). SUVR minus 1 correlated well with MRTMO [Formula: see text] (r(2) > 0.97). However, BPND by the single-input models did not correlate with [Formula: see text] by the dual-input graphical model (r(2) = 0.04). CONCLUSION: The dual-input graphical model [Formula: see text] is consistent with the reference tissue [Formula: see text] and SUVR-1, suggesting that these parameters can accurately quantify binding of (11)C-PBB3 despite the entry of its radiometabolites into the brain.
Authors: Hiroto Kuwabara; Robert A Comley; Edilio Borroni; Michael Honer; Kelly Kitmiller; Joshua Roberts; Lorena Gapasin; Anil Mathur; Gregory Klein; Dean F Wong Journal: J Nucl Med Date: 2018-08-10 Impact factor: 10.057
Authors: Michel Koole; Talakad G Lohith; John L Valentine; Idriss Bennacef; Ruben Declercq; Tom Reynders; Kerry Riffel; Sofie Celen; Kim Serdons; Guy Bormans; Sandrine Ferry-Martin; Philippe Laroque; Abbas Walji; Eric D Hostetler; Richard J Briscoe; Jan de Hoon; Cyrille Sur; Koen Van Laere; Arie Struyk Journal: Mol Imaging Biol Date: 2020-02 Impact factor: 3.488
Authors: Dustin W Wooten; Nicolas J Guehl; Eline E Verwer; Timothy M Shoup; Daniel L Yokell; Nevena Zubcevik; Neil Vasdev; Ross D Zafonte; Keith A Johnson; Georges El Fakhri; Marc D Normandin Journal: J Nucl Med Date: 2016-09-22 Impact factor: 10.057
Authors: Daniel R Schonhaut; Corey T McMillan; Salvatore Spina; Bradford C Dickerson; Andrew Siderowf; Michael D Devous; Richard Tsai; Joseph Winer; David S Russell; Irene Litvan; Erik D Roberson; William W Seeley; Lea T Grinberg; Joel H Kramer; Bruce L Miller; Peter Pressman; Ilya Nasrallah; Suzanne L Baker; Stephen N Gomperts; Keith A Johnson; Murray Grossman; William J Jagust; Adam L Boxer; Gil D Rabinovici Journal: Ann Neurol Date: 2017-10 Impact factor: 10.422