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Kinetic Modeling of the Tau PET Tracer 18 F-AV-1451 in Human Healthy Volunteers and Alzheimer Disease Subjects.

Authors :
Barret O
Alagille D
Sanabria S
Comley RA
Weimer RM
Borroni E
Mintun M
Seneca N
Papin C
Morley T
Marek K
Seibyl JP
Tamagnan GD
Jennings D
Source :
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2017 Jul; Vol. 58 (7), pp. 1124-1131. Date of Electronic Publication: 2016 Dec 01.
Publication Year :
2017

Abstract

<superscript>18</superscript> F-AV-1451 is currently the most widely used of several experimental tau PET tracers. The objective of this study was to evaluate <superscript>18</superscript> F-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: <superscript>18</superscript> F-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 (BP <subscript>ND</subscript> ), and SUVR. BP <subscript>ND</subscript> 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 <superscript>18</superscript> F-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 R <superscript>2</superscript> > 0.93 was found between BP <subscript>ND</subscript> (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 <superscript>18</superscript> F-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 BP <subscript>ND</subscript> , whereas SUVR sensitivity to regional cerebral blood changes needs further investigation.<br /> (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Details

Language :
English
ISSN :
1535-5667
Volume :
58
Issue :
7
Database :
MEDLINE
Journal :
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Publication Type :
Academic Journal
Accession number :
27908967
Full Text :
https://doi.org/10.2967/jnumed.116.182881