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FältnamnIndikatorerMetadata
00005740naa a2200769 4500
001oai:gup.ub.gu.se/326674
003SwePub
008240528s2023 | |||||||||||000 ||eng|
0247 a https://gup.ub.gu.se/publication/3266742 URI
0247 a https://doi.org/10.2967/jnumed.122.2644342 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Tissot, C.4 aut
2451 0a The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of 18F MK6240 Tau PET in Target Regions
264 c 2022-11-17
264 1b Society of Nuclear Medicine,c 2023
520 a 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.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653 a Key Words
653 a tau
653 a PET
653 a reference region
653 a off-target binding
653 a [F-18]MK6240
653 a alzheimer-disease
653 a pathology
653 a Radiology
653 a Nuclear Medicine & Medical Imaging
7001 a Servaes, S.4 aut
7001 a Lussier, F. Z.4 aut
7001 a Ferrai-Souza, J. P.4 aut
7001 a Therriault, J.4 aut
7001 a Ferreirat, P. C.4 aut
7001 a Bezgin, G.4 aut
7001 a Bellaver, B.4 aut
7001 a Leffa, D. T.4 aut
7001 a Mathotaarachchi, S. S.4 aut
7001 a Chamoun, M.4 aut
7001 a Stevenson, J.4 aut
7001 a Rahmouni, N.4 aut
7001 a Kang, M. S.4 aut
7001 a Pallen, V.4 aut
7001 a Margherita-Poltronetti, N.4 aut
7001 a Wang, Y. T.4 aut
7001 a Fernandez-Arias, J.4 aut
7001 a Lessa Benedet, Andréau Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xlesan
7001 a Zimmer, E. R.4 aut
7001 a Soucy, J. P.4 aut
7001 a Tudorascu, D. L.4 aut
7001 a Cohen, A. D.4 aut
7001 a Sharp, M.4 aut
7001 a Gauthier, S.4 aut
7001 a Massarweh, G.4 aut
7001 a Lopresti, B.4 aut
7001 a Klunk, W. E.4 aut
7001 a Baker, S. L.4 aut
7001 a Villemagne, V. L.4 aut
7001 a Rosa-Neto, P.4 aut
7001 a Pascoal, T. A.4 aut
7102 a Göteborgs universitetb Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi4 org
7730 t Journal of Nuclear Medicined : Society of Nuclear Medicineg 64:3, s. 452-459q 64:3<452-459x 0161-5505x 2159-662X
8564 8u https://gup.ub.gu.se/publication/326674
8564 8u https://doi.org/10.2967/jnumed.122.264434

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