The Association of Age-Related and Off-Target Retention with Longitudinal Quantification of [ 18 F]MK6240 Tau PET in Target Regions.

Autor:	Tissot C; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada.; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Servaes S; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Lussier FZ; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Ferrari-Souza JP; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Graduate Program in Biological Sciences: Biochemistry, Porto Alegre, Brazil., Therriault J; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Ferreira PCL; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Bezgin G; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Bellaver B; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.; Graduate Program in Biological Sciences: Biochemistry, Porto Alegre, Brazil., Leffa DT; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Mathotaarachchi SS; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Chamoun M; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Stevenson J; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Rahmouni N; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Kang MS; Artificial Intelligence and Computational Neurosciences Lab, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.; L.C. Campbell Cognitive Neurology Unit, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada., Pallen V; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Margherita-Poltronetti N; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Wang YT; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Fernandez-Arias J; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada., Benedet AL; University of Gothenburg, Gothenburg, Sweden., Zimmer ER; Graduate Program in Biological Sciences: Biochemistry, Porto Alegre, Brazil.; Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Soucy JP; Montreal Neurological Institute, Montreal, Quebec, Canada., Tudorascu DL; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Cohen AD; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Sharp M; Montreal Neurological Institute, Montreal, Quebec, Canada., Gauthier S; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada.; Douglas Mental Health Institute, Montreal, Quebec, Canada., Massarweh G; Department of Radiochemistry, Montreal Neurological Institute, Montreal, Quebec, Canada., Lopresti B; Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and., Klunk WE; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Baker SL; Lawrence Berkeley National Laboratory, Berkeley, California., Villemagne VL; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania., Rosa-Neto P; McGill University, Montreal, Quebec, Canada.; McGill University Research Center for Studies in Aging, Montreal, Quebec, Canada.; Montreal Neurological Institute, Montreal, Quebec, Canada.; Douglas Mental Health Institute, Montreal, Quebec, Canada., Pascoal TA; Departments of Psychiatry and Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; pascoalt@upmc.edu.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2023 Mar; Vol. 64 (3), pp. 452-459. Date of Electronic Publication: 2022 Nov 17.
DOI:	10.2967/jnumed.122.264434
Abstrakt:	6-(fluoro- 18 F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([ 18 F]MK6240) tau PET tracer quantifies the brain tau neurofibrillary tangle load in Alzheimer disease. The aims of our study were to test the stability 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 [ 18 F]MK6240 in target regions. Methods: We assessed reference, target, age-related, and off-target regions in 125 individuals across the aging and Alzheimer disease spectrum with longitudinal [ 18 F]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 [ 18 F]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-β-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 associations between changes in region uptake, respectively. Results: Inferior cerebellar gray matter SUV did not differ on the basis of diagnosis and amyloid-β status, cross-sectionally and over time. [ 18 F]MK6240 uptake significantly differed between CUY and CU adults in the putamen or pallidum (affecting ∼75% of the region) and in the Braak II region (affecting ∼35%). Changes in meningeal and putamen or pallidum 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 stable over time and thus was deemed a suitable reference region for quantification. Despite not being visually perceptible, [ 18 F]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. Nevertheless, 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 [ 18 F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification. (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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