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Background and objective <p>In neuroinflammation, activated astrocytes, called reactive astrocytes, highly express monoamine oxidase B (MAO-B). [<sup>18</sup>F]SMBT-1 is a novel PET tracer developed for imaging neuroinflammation, with highly selective binding to MAO-B. The quantification method for [<sup>18</sup>F]SMBT-1 PET imaging has not been established, although some human studies using [<sup>18</sup>F]SMBT-1 PET imaging have already been conducted. In this study, we explored the most appropriate method for quantifying [<sup>18</sup>F]SMBT-1 PET.</p> Methods <p>Dynamic PET scanning of [<sup>18</sup>F]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.</p> Results <p>The values of the χ<sup>2</sup> 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&#xa0;min post-injection, were strongly correlated with Vt (r = 0.9188–0.9445, p &lt; 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 &lt; 0.0001).</p> Conclusions <p>These findings suggest that SUVR-1, especially at 50–70&#xa0;min and 70–90&#xa0;min post-injection, reflects MAO-B distribution and is useful for quantifying [<sup>18</sup>F]SMBT-1 PET imaging, potentially enabling noninvasive assessment of neuroinflammation in the brain.</p> Trial registration <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月15日

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  • Kotaro Hiraoka,
  • Berihu Mesfin,
  • Yingying Wu,
  • Yuki Shimizu,
  • Asuka Kikuchi,
  • Ryuichi Harada,
  • Aiko Ishiki,
  • Yoshihito Funaki,
  • Shozo Furumoto,
  • Shunji Mugikura,
  • Nobuyuki Okamura,
  • Akio Kikuchi,
  • Kazuhiko Yanai,
  • Hiroyuki Arai,
  • Hiroshi Watabe,
  • Manabu Tashiro

摘要

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.