18F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate 18F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods: 18F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BPND), and SUVR. BPND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results: AD demonstrated increased 18F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R2 > 0.93 was found between BPND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although 18F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BPND, whereas SUVR sensitivity to regional cerebral blood changes needs further investigation.
18F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate 18F-AV-1451 binding with full kinetic analysis using a metabolite-corrected arterial input function and to compare parameters derived from kinetic analysis with SUV ratio (SUVR) calculated over different imaging time intervals. Methods:18F-AV-1451 PET brain imaging was completed in 16 subjects: 4 young healthy volunteers (YHV), 4 aged healthy volunteers (AHV), and 8 Alzheimer disease (AD) subjects. Subjects were imaged for 3.5 h, with arterial blood samples obtained throughout. PET data were analyzed using plasma and reference tissue-based methods to estimate the distribution volume, binding potential (BPND), and SUVR. BPND and SUVR were calculated using the cerebellar cortex as a reference region and were compared across the different methods and across the 3 groups (YHV, AHV, and AD). Results:AD demonstrated increased 18F-AV-1451 retention compared with YHV and AHV based on both invasive and noninvasive analyses in cortical regions in which paired helical filament tau accumulation is expected in AD. A correlation of R2 > 0.93 was found between BPND (130 min) and SUVR-1 at all time intervals. Cortical SUVR curves reached a relative plateau around 1.0-1.2 for YHV and AHV by approximately 50 min, but increased in AD by up to approximately 20% at 110-130 min and approximately 30% at 160-180 min relative to 80-100 min. Distribution volume (130 min) was lower by 30%-35% in the YHV than AHV. Conclusion: Our data suggest that although 18F-AV-1451 SUVR curves do not reach a plateau and are still increasing in AD, an SUVR calculated over an imaging window of 80-100 min (as currently used in clinical studies) provides estimates of paired helical filament tau burden in good correlation with BPND, whereas SUVR sensitivity to regional cerebral blood changes needs further investigation.
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: Hugo Botha; William G Mantyh; Melissa E Murray; David S Knopman; Scott A Przybelski; Heather J Wiste; Jonathan Graff-Radford; Keith A Josephs; Christopher G Schwarz; Walter K Kremers; Bradley F Boeve; Ronald C Petersen; Mary M Machulda; Joseph E Parisi; Dennis W Dickson; Val Lowe; Clifford R Jack; David T Jones Journal: Brain Date: 2018-04-01 Impact factor: 13.501
Authors: Jennifer L Whitwell; Jonathan Graff-Radford; Nirubol Tosakulwong; Stephen D Weigand; Mary Machulda; Matthew L Senjem; Christopher G Schwarz; Anthony J Spychalla; David T Jones; Daniel A Drubach; David S Knopman; Bradley F Boeve; Nilüfer Ertekin-Taner; Ronald C Petersen; Val J Lowe; Clifford R Jack; Keith A Josephs Journal: Ann Neurol Date: 2018-02-06 Impact factor: 10.422
Authors: Sandra Sanabria Bohórquez; Jan Marik; Annie Ogasawara; Jeff N Tinianow; Herman S Gill; Olivier Barret; Gilles Tamagnan; David Alagille; Gai Ayalon; Paul Manser; Thomas Bengtsson; Michael Ward; Simon-Peter Williams; Geoffrey A Kerchner; John P Seibyl; Kenneth Marek; Robby M Weimer Journal: Eur J Nucl Med Mol Imaging Date: 2019-06-28 Impact factor: 9.236
Authors: Yun Zhou; Shaney Flores; Syahir Mansor; Russ C Hornbeck; Zhude Tu; Joel S Perlmutter; Beau Ances; John C Morris; Robert J Gropler; Tammie L S Benzinger Journal: Eur J Nucl Med Mol Imaging Date: 2021-02-18 Impact factor: 9.236