Assessing Reactive Astrogliosis with 18F-SMBT-1 Across the Alzheimer Disease Spectrum

Autor: Victor L. Villemagne, Ryuichi Harada, Vincent Doré, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Pierrick Bourgeat, Ying Xia, Simon Laws, Svetlana Bozinovski, Kun Huang, Milos D. Ikonomovic, Jürgen Fripp, Kazuhiko Yanai, Nobuyuki Okamura, Christopher C. Rowe
Rok vydání: 2022
Předmět:
Zdroj: J Nucl Med
ISSN: 2159-662X
0161-5505
DOI: 10.2967/jnumed.121.263255
Popis: A neuroinflammatory reaction in Alzheimer disease (AD) brains involves reactive astrocytes that overexpress monoamine oxidase-B (MAO-B). (18)F-(S)-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline ((18)F-SMBT-1) is a novel (18)F PET tracer highly selective for MAO-B. We characterized the clinical performance of (18)F-SMBT-1 PET across the AD continuum as a potential surrogate marker of reactive astrogliosis. Methods: We assessed (18)F-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. (18)F-SMBT-1 outcomes were expressed as SUV ratio using the subcortical white matter as a reference region. Results: (18)F-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 (18)F-SMBT-1 binding in the group with Aβ− mild cognitive impairment. Conversely, (18)F-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, (18)F-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, (18)F-SMBT-1 correlated strongly with Aβ burden and much less with tau burden. Although in most cortical regions (18)F-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. (18)F-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 (18)F-SMBT-1 showed that Aβ+ AD patients, but most importantly, Aβ+ CN individuals, had significantly higher regional (18)F-SMBT-1 binding than Aβ− CN individuals. Moreover, in several regions in the brain, (18)F-SMBT-1 retention was highly associated with Aβ load. These findings suggest that increased (18)F-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.
Databáze: OpenAIRE
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