Novel PET imaging agent detects earliest signs of Alzheimer’s disease

A new highly selective PET imaging agent can detect the presence of overexpressed monoamine oxidase-B (MAO-B) in cognitively unimpaired individuals with high beta amyloid (Aβ)—one of the earliest signs of Alzheimer’s disease—according to research published in the October issue of The Journal of Nuclear Medicine. The radiotracer, ¹⁸F-SMBT-1, allows for a better understanding of the role of inflammation in Alzheimer’s disease, which can enable more accurate staging and prognosis at earlier stages.

Brain inflammation that accompanies Alzheimer’s disease involves reactive astrocytes, which are cells that overexpress MAO-B. The newly developed ¹⁸F-SMBT-1 radiotracer is highly selective for MAO-B and as a result has increased binding to reactive astrocytes. “This increased binding suggests that ¹⁸F-SMBT-1 can potentially be used as a surrogate marker to detect reactive astrogliosis in Alzheimer’s disease,” noted Victor Villemagne, MD, professor of psychiatry at the University of Pittsburgh in Pittsburgh, Pennsylvania.

The study aimed to characterize ¹⁸F-SMBT-1 binding to reactive astrocytes across the Alzheimer’s disease continuum. Study participants included three clinical groups: 57 cognitively unimpaired controls, 12 subjects meeting criteria for mild cognitive impairment (MCI), and eight subjects meeting criteria for Alzheimer’s disease.

Participants underwent several types of imaging, including ¹⁸F-SMBT-1 PET, Aβ PET, tau PET, and MRI. Images were normalized and statistical analyses conducted to assess ¹⁸F-SMBT-1 binding in relation to Aβ and tau pathology burden. ¹⁸F-SMBT-1 was found to be highly correlated with Aβ burden, and much less with tau burden.

The three clinical groups were then classified based on their Aβ status (either as Aβ+ or Aβ-). No significant differences in ¹⁸F-SMBT-1 binding were found among Aβ- participants in the control and MCI groups. In the Aβ+ subjects with Alzheimer’s disease, ¹⁸F-SMBT-1 binding was significantly higher. Most importantly, ¹⁸F-SMBT-1 binding was significantly higher in the Aβ+ control group as compared to Aβ- control group.

“It’s of note that the brain regions where we saw this higher ¹⁸F-SMBT-1 binding in the control group are regions known for early Aβ deposition. This suggests that reactive astrocytes are associated with early Aβ deposition at the preclinical stages of Alzheimer’s disease and likely play a role over clinical progression,” said Villemagne.

He continued, “Implementation of ¹⁸F-SMBT-1 will clarify the role of reactive astrogliosis in neurodegenerative conditions, not just Alzheimer’s disease and its potential independent and/or synergistic effects on pathology, neurodegeneration, cognition, and disease progression. This has the potential to define and refine the diagnostic, staging and prognostic roles of reactive astrogliosis in these conditions.”

The authors of “Assessing reactive astrogliosis with ¹⁸F-SMBT-1 across the Alzheimer’s disease spectrum” include Victor L. Villemagne, Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, and Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Ryuichi Harada, Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan, and Institute of Development of Aging and Cancer, Tohoku University, Sendai, Japan; Vincent Doré, Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, and CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Melbourne, Australia; Shozo Furumoto, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan; Rachel Mulligan, Natasha Krishnadas, Svetlana Bozinovski, and Kun Huang, Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia; Yukitsuka Kudo, Institute of Development of Aging and Cancer, Tohoku University, Sendai, Japan; Samantha Burnham, CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Melbourne, Australia; Pierrick Bourgeat, Ying Xia, and Jürgen Fripp, CSIRO The Australian e-Health Research Centre, Brisbane, Australia; Simon Laws, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; Milos D. Ikonomovic, Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, and Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; Kazuhiko Yanai, Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan; Nobuyuki Okamura, Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Japan; and Christopher C. Rowe, Department of Molecular Imaging & Therapy, Austin Health, Melbourne, Australia, The Florey Institute of Neurosciences and Mental Health, The University of Melbourne, Melbourne, Australia, and The Australian Dementia Network.

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Journal: Journal of Nuclear Medicine
DOI: 10.2967/jnumed.121.263255
Article Title: Assessing reactive astrogliosis with 18F-SMBT-1 across the Alzheimer’s disease spectrum
Article Publication Date: 3-Oct-2022
COI Statement: Yukitsuka Kudo and Nobuyuki Okamura own stock in Clino Ltd., licensing SMBT-1. Ryuichi Harada, Shozo Furumoto, Yukitsuka Kudo, and Nobuyuki Okamura have a patent pending for the technology described in this article.

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