Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/31041
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dc.contributor.authorVillemagne, Victor L-
dc.contributor.authorHarada, Ryuichi-
dc.contributor.authorDoré, Vincent-
dc.contributor.authorFurumoto, Shozo-
dc.contributor.authorMulligan, Rachel S-
dc.contributor.authorKudo, Yukitsuka-
dc.contributor.authorBurnham, Samantha-
dc.contributor.authorKrishnadas, Natasha-
dc.contributor.authorBourgeat, Pierrick-
dc.contributor.authorXia, Ying-
dc.contributor.authorLaws, Simon-
dc.contributor.authorBozinovski, Svetlana-
dc.contributor.authorHuang, Kun-
dc.contributor.authorIkonomovic, Milos D-
dc.contributor.authorFripp, Jürgen-
dc.contributor.authorYanai, Kazuhiko-
dc.contributor.authorOkamura, Nobuyuki-
dc.contributor.authorRowe, Christopher C-
dc.date2022-
dc.date.accessioned2022-10-21T04:39:52Z-
dc.date.available2022-10-21T04:39:52Z-
dc.date.issued2022-10-
dc.identifier.citationJournal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine 2022; 63(10): 1560-1569en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/31041-
dc.description.abstractA neuroinflammatory reaction in Alzheimer disease (AD) brains involves reactive astrocytes that overexpress monoamine oxidase-B (MAO-B). 18F-(S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (18F-SMBT-1) is a novel 18F PET tracer highly selective for MAO-B. We characterized the clinical performance of 18F-SMBT-1 PET across the AD continuum as a potential surrogate marker of reactive astrogliosis. Methods: We assessed 18F-SMBT-1 PET regional binding in 77 volunteers (76 ± 5.5 y old; 41 women, 36 men) across the AD continuum: 57 who were cognitively normal (CN) (44 amyloid-β [Aβ]-negative [Aβ-] and 13 Aβ-positive [Aβ+]), 12 who had mild cognitive impairment (9 Aβ- and 3 Aβ+), and 8 who had AD dementia (6 Aβ+ and 2 Aβ-). All participants also underwent Aβ and tau PET imaging, 3-T MRI, and neuropsychologic evaluation. Tau imaging results were expressed in SUV ratios using the cerebellar cortex as a reference region, whereas Aβ burden was expressed in centiloids. 18F-SMBT-1 outcomes were expressed as SUV ratio using the subcortical white matter as a reference region. Results: 18F-SMBT-1 yielded high-contrast images at steady state (60-80 min after injection). When compared with the Aβ- CN group, there were no significant differences in 18F-SMBT-1 binding in the group with Aβ- mild cognitive impairment. Conversely, 18F-SMBT-1 binding was significantly higher in several cortical regions in the Aβ+ AD group but also was significantly lower in the mesial temporal lobe and basal ganglia. Most importantly, 18F-SMBT-1 binding was significantly higher in the same regions in the Aβ+ CN group as in the Aβ- CN group. When all clinical groups were considered together, 18F-SMBT-1 correlated strongly with Aβ burden and much less with tau burden. Although in most cortical regions 18F-SMBT-1 did not correlate with brain volumetrics, regions known for high MAO-B concentrations presented a direct association with hippocampal and gray matter volumes, whereas the occipital lobe was directly associated with white matter hyperintensity. 18F-SMBT-1 binding was inversely correlated with Mini Mental State Examination and the Australian Imaging Biomarkers and Lifestyle's Preclinical Alzheimer Cognitive Composite in some neocortical regions such as the frontal cortex, lateral temporal lobe, and supramarginal gyrus. Conclusion: Cross-sectional human PET studies with 18F-SMBT-1 showed that Aβ+ AD patients, but most importantly, Aβ+ CN individuals, had significantly higher regional 18F-SMBT-1 binding than Aβ- CN individuals. Moreover, in several regions in the brain, 18F-SMBT-1 retention was highly associated with Aβ load. These findings suggest that increased 18F-SMBT-1 binding is detectable at the preclinical stages of Aβ accumulation, providing strong support for its use as a surrogate marker of astrogliosis in the AD continuum.en
dc.language.isoeng
dc.subjectAlzheimer diseaseen
dc.subjectMAO-Ben
dc.subjectamyloiden
dc.subjectbrain imagingen
dc.subjectreactive astrogliosisen
dc.subjecttauen
dc.titleAssessing Reactive Astrogliosis with 18F-SMBT-1 Across the Alzheimer Disease Spectrum.en
dc.typeJournal Articleen
dc.identifier.journaltitleJournal of Nuclear Medicine: Official Publication, Society of Nuclear Medicineen
dc.identifier.affiliationThe Florey Institute of Neuroscience and Mental Healthen
dc.identifier.affiliationCSIRO Health and Biosecurity Flagship: Australian e-Health Research Centre, Melbourne, Victoria, Australiaen
dc.identifier.affiliationSchool of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australiaen
dc.identifier.affiliationCSIRO: Australian e-Health Research Centre, Brisbane, Queensland, Australiaen
dc.identifier.affiliationDepartment of Molecular Imaging and Therapy, Austin Health, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.en
dc.identifier.affiliationAustralian Dementia Network, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Pharmacology, School of Medicine, Tohoku University, Sendai, Japan.en
dc.identifier.affiliationCyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.en
dc.identifier.affiliationInstitute of Development of Aging and Cancer, Tohoku University, Sendai, Japan.en
dc.identifier.affiliationDivision of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan.en
dc.identifier.affiliationMedicine (University of Melbourne)en
dc.identifier.doi10.2967/jnumed.121.263255en
dc.type.contentTexten
dc.identifier.pubmedid35086892
local.name.researcherBozinovski, Svetlana
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptMolecular Imaging and Therapy-
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