The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/259133 |
Resumo: | 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 stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and offtarget retention on the longitudinal quantification of [18F]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 [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean 6 SD, 2.25 6 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 6 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-b–negative and tau-negative, 58.50 6 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-b status, cross-sectionally and over time. [18F]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, [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. 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 [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification. |
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Tissot, CecileBellaver, BrunaZimmer, Eduardo RigonPascoal, Tharick Ali2023-06-17T03:37:56Z20230161-5505http://hdl.handle.net/10183/2591330011680406-(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 stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and offtarget retention on the longitudinal quantification of [18F]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 [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean 6 SD, 2.25 6 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 6 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-b–negative and tau-negative, 58.50 6 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-b status, cross-sectionally and over time. [18F]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, [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. 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 [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification.application/pdfengJournal of nuclear medicine. Reston, VA. Vol. 64, no. 3 (Mar. 2023), p. 452-459Doenças neurodegenerativasDoença de AlzheimerCerebeloProteínas tauEmaranhados neurofibrilaresTauPETReference regionOff-target binding[18F]MK6240The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regionsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001168040.pdf.txt001168040.pdf.txtExtracted Texttext/plain42640http://www.lume.ufrgs.br/bitstream/10183/259133/2/001168040.pdf.txt50df98b089483e3f305073fa4d48d264MD52ORIGINAL001168040.pdfTexto completo (inglês)application/pdf1315948http://www.lume.ufrgs.br/bitstream/10183/259133/1/001168040.pdf3f693a7bba5258a21f0fdf1a5162e77fMD5110183/2591332023-06-18 03:52:34.22413oai:www.lume.ufrgs.br:10183/259133Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-06-18T06:52:34Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
title |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
spellingShingle |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions Tissot, Cecile Doenças neurodegenerativas Doença de Alzheimer Cerebelo Proteínas tau Emaranhados neurofibrilares Tau PET Reference region Off-target binding [18F]MK6240 |
title_short |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
title_full |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
title_fullStr |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
title_full_unstemmed |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
title_sort |
The association of age-related and off-target retention with longitudinal quantification of [18F]MK6240 tau PET in target regions |
author |
Tissot, Cecile |
author_facet |
Tissot, Cecile Bellaver, Bruna Zimmer, Eduardo Rigon Pascoal, Tharick Ali |
author_role |
author |
author2 |
Bellaver, Bruna Zimmer, Eduardo Rigon Pascoal, Tharick Ali |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Tissot, Cecile Bellaver, Bruna Zimmer, Eduardo Rigon Pascoal, Tharick Ali |
dc.subject.por.fl_str_mv |
Doenças neurodegenerativas Doença de Alzheimer Cerebelo Proteínas tau Emaranhados neurofibrilares |
topic |
Doenças neurodegenerativas Doença de Alzheimer Cerebelo Proteínas tau Emaranhados neurofibrilares Tau PET Reference region Off-target binding [18F]MK6240 |
dc.subject.eng.fl_str_mv |
Tau PET Reference region Off-target binding [18F]MK6240 |
description |
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 stability of common reference region estimates in the cerebellum over time and across diagnoses and evaluate the effects of age-related and offtarget retention on the longitudinal quantification of [18F]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 [18F]MK6240 SUVs and SUV ratios (SUVRs) (mean 6 SD, 2.25 6 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 6 3.33 y) and 27 cognitively unimpaired older (CU) adults (amyloid-b–negative and tau-negative, 58.50 6 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-b status, cross-sectionally and over time. [18F]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, [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. 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 [18F]MK6240 signal, and in vivo studies should further explore its impact on tracer quantification. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-06-17T03:37:56Z |
dc.date.issued.fl_str_mv |
2023 |
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Estrangeiro info:eu-repo/semantics/article |
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Journal of nuclear medicine. Reston, VA. Vol. 64, no. 3 (Mar. 2023), p. 452-459 |
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