Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Journal of Nuclear Medicine

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • Follow JNM on Twitter
  • Visit JNM on Facebook
  • Join JNM on LinkedIn
  • Subscribe to our RSS feeds
OtherClinical Investigations (Human)

First-in-human evaluation of 18F-SMBT-1, a novel 18F-labeled MAO-B PET tracer for imaging reactive astrogliosis

Victor L Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J Lopresti, Kazuhiko Yanai, Christopher C Rowe and Nobuyuki Okamura
Journal of Nuclear Medicine February 2022, jnumed.121.263254; DOI: https://doi.org/10.2967/jnumed.121.263254
Victor L Villemagne
1 Department of Psychiatry, University of Pittsburgh, United States;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryuichi Harada
2 Department of Pharmacology, Tohoku University School of Medicine, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Dore
3 CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shozo Furumoto
4 Cyclotron and Radioisotope Center, Tohoku University, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rachel Mulligan
5 Department of Molecular Imaging & Therapy, Austin Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukitsuka Kudo
6 Institute of Development of Aging and Cancer, Tohoku University, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samantha Burnham
3 CSIRO Health and Biosecurity Flagship: The Australian e-Health Research Centre, Australia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Natasha Krishnadas
5 Department of Molecular Imaging & Therapy, Austin Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svetlana Bozinovski
5 Department of Molecular Imaging & Therapy, Austin Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kun Huang
5 Department of Molecular Imaging & Therapy, Austin Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian J Lopresti
7 University of Pittsburgh;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiko Yanai
2 Department of Pharmacology, Tohoku University School of Medicine, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher C Rowe
5 Department of Molecular Imaging & Therapy, Austin Health;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nobuyuki Okamura
8 Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

Background: Reactive gliosis changes, characterized by reactive astrocytes and activated microglia, contribute greatly to neurodegeneration throughout the course of Alzheimer’s disease (AD). Reactive astrocytes overexpress monoamine oxidase-B (MAO-B). We characterized the clinical performance of 18F-SMBT-1, a novel MAO-B PET tracer as a potential surrogate marker of reactive astrogliosis. Methods: Seventy-seven participants –53 controls (CN), 7 mild cognitively impaired (MCI), 7 AD patients, and 10 young controls (YCN)– were recruited for the different aspects of the study. Older participants underwent 3D-MPRAGE MRI and Aβ, tau, and 18F-SMBT-1 imaging with PET. To ascertain 18F-SMBT-1 selectivity to MAO-B, 9 participants underwent two 18F-SMBT-1 scans, before and after receiving 5mg selegiline twice daily for 5 days. To compare selectivity, 18F-THK5351 studies were also conducted before and after selegiline. Aβ burden was expressed in Centiloids. 18F-SMBT-1 outcomes were expressed as standard uptake value, as well as tissue ratios and binding parameters using the subcortical white matter as reference region. Results: 18F-SMBT-1 showed robust entry into the brain and reversible binding kinetics, with high tracer retention in basal ganglia, intermediate in cortical regions, and lowest in cerebellum and white matter which tightly follows the known regional brain distribution of MAO-B (R2=0.84). More than 85% of 18F-SMBT-1 signal was blocked by selegiline across the brain and, in contrast to 18F-THK5351, no residual cortical activity was observed after the selegiline regimen, indicating high selectivity for MAO-B and low non-specific binding. 18F-SMBT-1 also captured the known MAO-B increases with age, with an annual rate of change (~2.6%/yr), similar to the in vitro rates of change (~1.9%/yr). Quantitative and semiquantitative measures of 18F-SMBT-1 binding were highly associated (R2>0.94), suggesting a simplified tissue ratio approach could be used to generate outcome measures. Conclusion: 18F-SMBT-1 is a highly selective MAO-B tracer, with low non-specific binding, high entry into the brain and displaying reversible kinetics. Moreover, 18F-SMBT-1 brain distribution matches the reported in vitro distribution and captures the known MAO-B increases with age, suggesting 18F-SMBT-1 can potentially be used as a surrogate marker of reactive astrogliosis. Further validation of these findings with 18F-SMBT-1 will require examination of a much larger series, including participants with MCI and AD.

  • Molecular Imaging
  • MRI
  • Neurology
  • Amyloid
  • MAO-B
  • Neurodegeneration
  • Reactive astrogliosis
  • Tau
  • Copyright © 2022 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

SNMMI members

SNMMI Member Login

Login to the site using your SNMMI member credentials

Individuals

Non-Member Login

Login as an individual user

PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 63, Issue 5
May 1, 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Complete Issue (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
First-in-human evaluation of 18F-SMBT-1, a novel 18F-labeled MAO-B PET tracer for imaging reactive astrogliosis
(Your Name) has sent you a message from Journal of Nuclear Medicine
(Your Name) thought you would like to see the Journal of Nuclear Medicine web site.
Citation Tools
First-in-human evaluation of 18F-SMBT-1, a novel 18F-labeled MAO-B PET tracer for imaging reactive astrogliosis
Victor L Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J Lopresti, Kazuhiko Yanai, Christopher C Rowe, Nobuyuki Okamura
Journal of Nuclear Medicine Feb 2022, jnumed.121.263254; DOI: 10.2967/jnumed.121.263254

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
First-in-human evaluation of 18F-SMBT-1, a novel 18F-labeled MAO-B PET tracer for imaging reactive astrogliosis
Victor L Villemagne, Ryuichi Harada, Vincent Dore, Shozo Furumoto, Rachel Mulligan, Yukitsuka Kudo, Samantha Burnham, Natasha Krishnadas, Svetlana Bozinovski, Kun Huang, Brian J Lopresti, Kazuhiko Yanai, Christopher C Rowe, Nobuyuki Okamura
Journal of Nuclear Medicine Feb 2022, jnumed.121.263254; DOI: 10.2967/jnumed.121.263254
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

Clinical Investigations (Human)

  • Using, 68Ga-PSMA-11 PET/CT for therapy response assessment in patients with metastatic castration-resistant prostate cancer: an application of EAU/EANM recommendations in clinical practice.
  • Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer
  • 68Ga-PSMA-11 PET/MRI in patients with newly diagnosed intermediate or high-risk prostate adenocarcinoma: PET findings correlate with outcomes after definitive treatment
Show more Clinical Investigations (Human)

Clinical (Neurology)

  • 18F-PI-2620 Tau PET Improves the Imaging Diagnosis of Progressive Supranuclear Palsy
  • Differential diagnosis of parkinsonism based on deep metabolic imaging indices
  • Posterior Cingulate Involvement Does Not Argue Against LATE
Show more Clinical (Neurology)

Similar Articles

Keywords

  • molecular imaging
  • MRI
  • Neurology
  • amyloid
  • MAO-B
  • Neurodegeneration
  • Reactive astrogliosis
  • tau
SNMMI

© 2022 Journal of Nuclear Medicine

Powered by HighWire