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Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function.
J Nucl Med. 2017 09; 58(9):1483-1489.JN

Abstract

Increased brain uptake of 18F-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-min 18F-AV45 (291 ± 67 MBq) and 1-min 15O-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 VT was 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 by 15O-H2O SUV. Data are presented as mean ± SEM.

Results:

There was rapid metabolization of 18F-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%). VT correlated 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 of 18F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVRWM is better correlated with VT and more closely reflects VT differences between aMCI and AD than SUVRCB.

Authors+Show Affiliations

Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. Developmental and Lifespan Psychology, Vrije Universiteit Brussel, Brussels, Belgium.Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium.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.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.Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.Department of Neurology, University Hospital Brussels, Brussels, Belgium.Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium.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.Molecular Imaging Center Antwerp, University of Antwerp, Antwerp, Belgium steven.staelens@uantwerpen.be.

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

28336779

Citation

Ottoy, Julie, et al. "Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET By Pharmacokinetic Modeling With an Arterial Input Function." Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, vol. 58, no. 9, 2017, pp. 1483-1489.
Ottoy J, Verhaeghe J, Niemantsverdriet E, et al. Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function. J Nucl Med. 2017;58(9):1483-1489.
Ottoy, J., Verhaeghe, J., Niemantsverdriet, E., Wyffels, L., Somers, C., De Roeck, E., Struyfs, H., Soetewey, F., Deleye, S., Van den Bossche, T., Van Mossevelde, S., Ceyssens, S., Versijpt, J., Stroobants, S., Engelborghs, S., & Staelens, S. (2017). Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function. Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine, 58(9), 1483-1489. https://doi.org/10.2967/jnumed.116.184481
Ottoy J, et al. Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET By Pharmacokinetic Modeling With an Arterial Input Function. J Nucl Med. 2017;58(9):1483-1489. PubMed PMID: 28336779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validation of the Semiquantitative Static SUVR Method for 18F-AV45 PET by Pharmacokinetic Modeling with an Arterial Input Function. AU - Ottoy,Julie, AU - Verhaeghe,Jeroen, AU - Niemantsverdriet,Ellis, AU - Wyffels,Leonie, AU - Somers,Charisse, AU - De Roeck,Ellen, AU - Struyfs,Hanne, AU - Soetewey,Femke, AU - Deleye,Steven, AU - Van den Bossche,Tobi, AU - Van Mossevelde,Sara, AU - Ceyssens,Sarah, AU - Versijpt,Jan, AU - Stroobants,Sigrid, AU - Engelborghs,Sebastiaan, AU - Staelens,Steven, Y1 - 2017/03/23/ PY - 2016/09/21/received PY - 2017/03/06/accepted PY - 2017/3/25/pubmed PY - 2017/10/4/medline PY - 2017/3/25/entrez KW - 18F-AV45 KW - Alzheimer’s disease KW - amyloid KW - cerebral perfusion KW - kinetic modeling SP - 1483 EP - 1489 JF - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JO - J. Nucl. Med. VL - 58 IS - 9 N2 - Increased brain uptake of 18F-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-min 18F-AV45 (291 ± 67 MBq) and 1-min 15O-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 VT was 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 by 15O-H2O SUV. Data are presented as mean ± SEM. Results: There was rapid metabolization of 18F-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%). VT correlated 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 of 18F-AV45 assessed by the simplified static SUVR protocol does not truly reflect Aβ load. However, SUVRWM is better correlated with VT and more closely reflects VT differences between aMCI and AD than SUVRCB. SN - 1535-5667 UR - https://www.unboundmedicine.com/medline/citation/28336779/Validation_of_the_Semiquantitative_Static_SUVR_Method_for_18F_AV45_PET_by_Pharmacokinetic_Modeling_with_an_Arterial_Input_Function_ L2 - http://jnm.snmjournals.org/cgi/pmidlookup?view=long&amp;pmid=28336779 DB - PRIME DP - Unbound Medicine ER -