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The Association of ...
The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of 18F MK6240 Tau PET in Target Regions
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Tissot, C. (author)
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Servaes, S. (author)
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Lussier, F. Z. (author)
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Ferrai-Souza, J. P. (author)
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Therriault, J. (author)
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Ferreirat, P. C. (author)
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Bezgin, G. (author)
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Bellaver, B. (author)
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Leffa, D. T. (author)
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Mathotaarachchi, S. S. (author)
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Chamoun, M. (author)
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Stevenson, J. (author)
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Rahmouni, N. (author)
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Kang, M. S. (author)
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Pallen, V. (author)
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Margherita-Poltronetti, N. (author)
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Wang, Y. T. (author)
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Fernandez-Arias, J. (author)
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- Lessa Benedet, Andréa (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Zimmer, E. R. (author)
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Soucy, J. P. (author)
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Tudorascu, D. L. (author)
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Cohen, A. D. (author)
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Sharp, M. (author)
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Gauthier, S. (author)
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Massarweh, G. (author)
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Lopresti, B. (author)
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Klunk, W. E. (author)
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Baker, S. L. (author)
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Villemagne, V. L. (author)
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Rosa-Neto, P. (author)
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Pascoal, T. A. (author)
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(creator_code:org_t)
- 2022-11-17
- 2023
- English.
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 64:3, s. 452-459
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Abstract
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- 6-(fluoro-18F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([18F] MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stabil-ity of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and off -target retention on the longitudinal quantification of [18F]MK6240 in tar-get regions. Methods: We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzhei-mer disease spectrum with longitudinal [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean +/- SD, 2.25 +/- 0.40 y of follow-up). We obtained SUVR from meninges, exhibiting frequent off-target retention with [18F]MK6240. Additionally, we compared tracer uptake between 37 cognitively unimpaired young (CUY) (mean age, 23.41 +/- 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-P-negative and tau-negative, 58.50 +/- 9.01 y) to identify possible nonvisually apparent, age-related signal. Two-tailed t testing and Pearson correlation testing were used to determine the difference between groups and associa-tions between changes in region uptake, respectively. Results: Inferior cerebellar gray matter SUV did not differ on the basis of diagnosis and amyloid-P status, cross-sectionally and over time. [18F]MK6240 uptake significantly differed between CUY and CU adults in the puta-men or pallidum (affecting-75% of the region) and in the Braak II region (affecting-35%). Changes in meningeal and putamen or palli-dum SUVRs did not significantly differ from zero, nor did they vary across diagnostic groups. We did not observe significant correlations between longitudinal changes in age-related or meningeal off-target retention and changes in target regions, whereas changes in all target regions were strongly correlated. Conclusion: Inferior cerebellar gray matter was similar across diagnostic groups cross-sectionally and sta-ble over time and thus was deemed a suitable reference region for quantification. Despite not being visually perceptible, [18F]MK6240 has age-related retention in subcortical regions, at a much lower magnitude but topographically colocalized with significant off-target signal of the first-generation tau tracers. The lack of correlation between changes in age-related or meningeal and target retention suggests little influence of possible off-target signals on longitudinal tracer quantification. Nev-ertheless, the age-related retention in the Braak II region needs to be further investigated. Future postmortem studies should elucidate the source of the newly reported age-related [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Key Words
- tau
- PET
- reference region
- off-target binding
- [F-18]MK6240
- alzheimer-disease
- pathology
- Radiology
- Nuclear Medicine & Medical Imaging
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Tissot, C.
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Servaes, S.
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Lussier, F. Z.
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Ferrai-Souza, J. ...
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Therriault, J.
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Ferreirat, P. C.
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show more...
-
Bezgin, G.
-
Bellaver, B.
-
Leffa, D. T.
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Mathotaarachchi, ...
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Chamoun, M.
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Stevenson, J.
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Rahmouni, N.
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Kang, M. S.
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Pallen, V.
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Margherita-Poltr ...
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Wang, Y. T.
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Fernandez-Arias, ...
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Lessa Benedet, A ...
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Zimmer, E. R.
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Soucy, J. P.
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Tudorascu, D. L.
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Cohen, A. D.
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Sharp, M.
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Gauthier, S.
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Massarweh, G.
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Lopresti, B.
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Klunk, W. E.
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Baker, S. L.
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Villemagne, V. L ...
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Rosa-Neto, P.
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Pascoal, T. A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Journal of Nucle ...
- By the university
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University of Gothenburg