Kinetic and quantitative analysis of [18F]SMBT-1 PET imaging for monoamine oxidase B.

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.