PURPOSE: Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer's disease (AD) brain tissue; however, their spatiotemporal dynamics in vivo remain poorly understood. This multicenter study aimed to investigate the progression of astrocyte reactivity across the AD continuum, including healthy controls (HC), mild cognitive impairment (MCI), and AD, using the novel monoamine oxidase B (MAO-B)-specific PET tracer [18F]SMBT-1, while exploring its association with cognitive performance and amyloid burden. METHODS: A total of 91 participants (35 HC, 44 MCI, 12 AD) underwent [18F]SMBT-1 PET, amyloid PET, T1-weighted MRI, and standardized neuropsychological assessments. Standardized uptake value ratios (SUVRs) were calculated based on [18F]SMBT-1 PET data using four reference regions for subgroup comparisons stratified by Aβ status. RESULTS: [18F]SMBT-1 uptake was significantly elevated in amyloid-positive MCI (MCI+) and AD groups compared with amyloid-negative HC (HC-) in the frontal, temporal, and posterior cingulate regions. Notably, astrogliosis patterns distinguished MCI subtypes: MCI+ individuals exhibited a widespread AD-like pattern, whereas the MCI- group showed a distinct profile. Furthermore, the uptake in symptomatic MCI+ individuals was significantly higher than that in asymptomatic HC+ individuals. Regional SMBT-1 uptake also strongly correlated with greater Aβ burden and worse cognitive scores. CONCLUSION: This study demonstrates that [18F]SMBT-1 is a promising tool for characterizing the spatial pattern and magnitude of reactive astrogliosis across the Aβ-defined AD continuum. Our findings further suggest that astrogliosis may represent an important mechanistic link between amyloid pathology and cognitive impairment, supporting its potential relevance in therapeutic development. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs031210602, registered Feb. 07, 2022. URL FOR THE TRIAL REGISTRY: https://jrct.mhlw.go.jp/en-latest-detail/jRCTs031210602 .

OBJECTIVE: [18F]SMBT-1 is a selective and reversible monoamine oxidase B (MAO-B) radiotracer used for astrogliosis imaging. This study aimed to observe the whole-body biodistribution of [¹⁸F]SMBT-1 and evaluate peripheral MAO-B expression in healthy human volunteers using dynamic positron emission tomography (PET) imaging. METHODS: Six healthy subjects (four males, two females; age range: 21–63 years) underwent nine dynamic PET scans over 5.5 h after [18F]SMBT-1 injection. The first five emission scans were acquired consecutively in a single session within 30 min (min) of post-injection (p.i.). The remaining four emission scans were performed at 70–110, 150–180, 220–250, and 290–330 min p.i. Regions of interest (ROIs) were manually drawn on the co-registered PET and magnetic resonance imaging (MRI) for the selected organs to extract mean standardized uptake values (SUVmean) and generate time-activity curves (TACs). RESULTS: A significantly high early uptake of [18F]SMBT-1 was observed in the kidneys, liver, heart, and stomach between 5 and 30 min p.i. The kidneys showed the highest early peak at 5 min p.i. (SUVmean = 14.2 ± 3.5). The gallbladder and intestines exhibited a delayed uptake pattern, with the gallbladder SUVmean increasing substantially from 9.0 ± 4.2 at 30 min to 123.7 ± 53.4 at 330 min. No significant differences in tracer uptake patterns were observed across participants. CONCLUSION: [¹⁸F]SMBT-1 exhibited favorable reversible kinetics in the whole-body biodistribution assessment, confirming its established utility for imaging reactive astrocytes and indicating its potential for future applications in systemic high MAO-B-related pathologies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12149-025-02144-2.

BACKGROUND AND OBJECTIVE: In neuroinflammation, activated astrocytes, called reactive astrocytes, highly express monoamine oxidase B (MAO-B). [18F]SMBT-1 is a novel PET tracer developed for imaging neuroinflammation, with highly selective binding to MAO-B. The quantification method for [18F]SMBT-1 PET imaging has not been established, although some human studies using [18F]SMBT-1 PET imaging have already been conducted. In this study, we explored the most appropriate method for quantifying [18F]SMBT-1 PET. METHODS: Dynamic PET scanning of [18F]SMBT-1, accompanied by serial arterial blood sampling, was performed in healthy elderly subjects. With PET and blood data, the total distribution volumes (Vts) in the brain regions were calculated using a one-tissue compartment model (1TCM), a two-tissue compartment model (2TCM), and Logan graphical analysis. Standardized uptake values (SUVs) and SUV ratio-1 (SUVR-1) were determined for different time frames and reference regions. RESULTS: The values of the χ2 criterion and Akaike's Information Criterion (AIC) in the brain regions were lower in 2TCM than in 1TCM, suggesting that 2TCM was a better model in terms of curve fitting. However, the very high coefficient of variation (%COV) for parameters such as K1, k2, k3, and k4 in 2TCM suggests that these parameters may not have been properly estimated. SUVs, especially at 50-70 and 70-90 min post-injection, were strongly correlated with Vt (r = 0.9188-0.9445, p < 0.0001). SUVR-1 at these time points, referenced to various regions, showed significant correlations with MAO-B distribution in the brain shown in a previous postmortem study (r = 0.9362-0.9399, p < 0.0001). CONCLUSIONS: These findings suggest that SUVR-1, especially at 50-70 min and 70-90 min post-injection, reflects MAO-B distribution and is useful for quantifying [18F]SMBT-1 PET imaging, potentially enabling noninvasive assessment of neuroinflammation in the brain. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) (jRCTs021200019). It was registered on August 25, 2020. The jRCT was approved as a member of the Primary Registry Network of the WHO ICTRP.

Age-related deterioration in positron emission tomography (PET) systems can be monitored using cross-calibration scans for scanner calibration. This study aimed to evaluate changes in the sensitivity of a PET system over time using routinely collected cross-calibration factor (CCF) measurement data and NEMA sensitivity measurement data acquired at our facility. We used CCF measurement data acquired over eight years, from 2016 to 2023. The count rates were calculated from raw data. The NEMA sensitivity measurements were also performed in 2017 and 2024 to compare with the sensitivities obtained from the CCF measurements. The PET images were reconstructed using the CCF data. A region of interest (ROI) was placed at the center of the PET images and count rates from the PET images were obtained. The sensitivity changes in the CCF data showed a linear decrease in sensitivity over eight years, with a mean annual reduction rate of approximately 2.0%. A comparison of the NEMA sensitivity measurements indicated a decrease in sensitivity, with a 12% reduction over eight eight years. The sensitivity was higher at the center of the axial field of view than at the edges. The ROI data also showed a linear decrease in sensitivity. This is consistent with the CCF data. Additionally, the coefficient of variation increased towards the edge of the slice. By utilizing the CCF measurement data, we obtained age-related changes in the PET system, suggesting that the PET system used in our facility may experience an annual sensitivity deterioration of approximately 2.0%.