RT Journal Article SR Electronic T1 Assessing reactive astrogliosis with 18F-SMBT-1 across the Alzheimer’s disease spectrum JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.121.263255 DO 10.2967/jnumed.121.263255 A1 Victor L Villemagne A1 Ryuichi Harada A1 Vincent Dore A1 Shozo Furumoto A1 Rachel Mulligan A1 Yukitsuka Kudo A1 Samantha Burnham A1 Natasha Krishnadas A1 Pierrick Bourgeat A1 Ying Xia A1 Simon Laws A1 Svetlana Bozinovski A1 Kun Huang A1 Milos D Ikonomovic A1 Jurgen Fripp A1 Kazuhiko Yanai A1 Nobuyuki Okamura A1 Christopher C Rowe YR 2022 UL http://jnm.snmjournals.org/content/early/2022/02/03/jnumed.121.263255.abstract AB Background: Neuroinflammatory reaction in Alzheimer’s disease (AD) brains involves reactive astrocytes which overexpress monoamine oxidase-B (MAO-B). 18F-SMBT-1 is a novel F-18 PET tracer highly selective for MAO-B. We characterized the clinical performance of 18F-SMBT-1 PET across the Alzheimer’s disease (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.o.; 41F/36M) across the AD continuum: 57 cognitively unimpaired controls (CN, 44 Aβ- & 13 Aβ+), 12 mild cognitively impaired (MCI, 9 Aβ- & 3 Aβ+), and 8 AD dementia patients (6 Aβ+ and 2 Aβ-). All participants also underwent Aβ and tau PET imaging, 3T MRI and neuropsychological evaluation. Tau imaging results were expressed in standard uptake value ratios (SUVR) using the cerebellar cortex as reference region, while Aβ burden was expressed in Centiloids. 18F-SMBT-1 outcomes were expressed as SUVR using the subcortical white matter as reference region. Results: 18F-SMBT-1 yielded high contrast images at steady state (60-80 min after injection). When compared to Aβ-CN, there were no significant differences in 18F-SMBT-1 binding in the Aβ-MCI group. Conversely, 18F-SMBT-1 binding was significantly higher in several cortical regions in the Aβ+AD group, but also was significantly lower in mesial temporal and basal ganglia. Most importantly, 18F-SMBT-1 binding was significantly higher in the same regions in Aβ+CN when compared to Aβ-CN. When all clinical groups were considered together, 18F-SMBT-1 was highly correlated with Aβ burden, and much less with tau burden. While in most cortical regions 18F-SMBT-1 was not correlated with brain volumetrics, regions known for high MAO-B concentrations presented a direct association with hippocampal and grey matter volumes, while the occipital lobe was directly associated with white matter hyperintensities. 18F-SMBT-1 binding was inversely correlated with MMSE and AIBL PACC in some neocortical regions such as the frontal cortex, lateral temporal and supramarginal gyrus. Conclusion: Cross-sectional human PET studies with 18F-SMBT-1, showed that Aβ+AD, but most importantly, Aβ+CN have significantly higher regional 18F-SMBT-1 binding than Aβ- CN. 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 surrogate marker of astrogliosis in the AD continuum.