Validation of the Semiquantitative Static SUVR Method for18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function.
Increased brain uptake of18F-AV45 visualized by PET is a key biomarker for Alzheimer disease (AD). The SUV ratio (SUVR) is widely used for quantification, but is subject to variability based on choice of reference region and changes in cerebral blood flow. Here we validate the SUVR method against the gold standard volume of distribution (VT) to assess cross-sectional differences in plaque load.Methods:Dynamic 60-min18F-AV45 (291 ± 67 MBq) and 1-min15O-H2O (370 MBq) scans were obtained in 35 age-matched elderly subjects, including 10 probable AD, 15 amnestic mild cognitive impairment (aMCI), and 10 cognitively healthy controls (HCs).18F-AV45 VTwas determined from 2-tissue-compartment modeling using a metabolite-corrected plasma input function. Static SUVR was calculated at 50-60 min after injection, using either cerebellar gray matter (SUVRCB) or whole subcortical white matter (SUVRWM) as the reference. Additionally, whole cerebellum, pons, centrum semiovale, and a composite region were examined as alternative references. Blood flow was quantified by15O-H2O SUV. Data are presented as mean ± SEM.Results:There was rapid metabolization of18F-AV45, with only 35% of unchanged parent remaining at 10 min. Compared with VT, differences in cortical Aβ load between aMCI and AD were overestimated by SUVRWM(+4% ± 2%) and underestimated by SUVRCB(-10% ± 2%). VTcorrelated better with SUVRWM(Pearson r: from 0.63 for posterior cingulate to 0.89 for precuneus,P< 0.0001) than with SUVRCB(Pearson r: from 0.51 for temporal lobe [P= 0.002] to 0.82 for precuneus [P< 0.0001]) in all tested regions. Correlation results for the alternative references were in between those for CB and WM.15O-H2O data showed that blood flow was decreased in AD compared with aMCI in cortical regions (-5% ± 1%) and in the reference regions (CB, -9% ± 8%; WM, -8% ± 8%).Conclusion:Increased brain uptake of18F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVRWMis better correlated with VTand more closely reflects VTdifferences between aMCI and AD than SUVRCB.
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
Julie
J
Ottoy
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
Jeroen
J
Verhaeghe
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Ellis
E
Niemantsverdriet
Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
Leonie
L
Wyffels
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Charisse
C
Somers
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Developmental and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.
Ellen
E
De Roeck
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Hanne
H
Struyfs
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Femke
F
Soetewey
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.
Steven
S
Deleye
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Molecular Genetics, VIB, University of Antwerp, Antwerp, Belgium.|Department of Neurology, Antwerp University Hospital, Edegem, Belgium.|Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; and.
Tobi
T
Van den Bossche
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Molecular Genetics, VIB, University of Antwerp, Antwerp, Belgium.|Department of Neurology, Antwerp University Hospital, Edegem, Belgium.|Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; and.
Sara
S
Van Mossevelde
Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
Sarah
S
Ceyssens
Department of Neurology, University Hospital Brussels, Brussels, Belgium.
Jan
J
Versijpt
Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.
Sigrid
S
Stroobants
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium; and.
Sebastiaan
S
Engelborghs
Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium steven.staelens@uantwerpen.be.
Steven
S
Staelens
D000368:Aged; D000814:Aniline Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D001692:Biological Transport; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D002560:Cerebrovascular Circulation; D005026:Ethylene Glycols / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography
D000814:Aniline Compounds; D005026:Ethylene Glycols; C545186:florbetapir
18F-AV45; Alzheimer’s disease; amyloid; cerebral perfusion; kinetic modeling