Skip to main content

Main menu

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

Liver and Brain Levels of 11β-hydroxysteroid Dehydrogenase Type 1 Enzyme in Obesity: Preliminary Results from PET Imaging Studies

Jason Bini, Jean-Dominique Gallezot, Songye Li, Keunpoong Lim, Paul Emery, Michael Kapinos, Jim Ropchan, Nabeel Nabulsi, Ania Jastreboff, Yiyun Huang and Richard Carson
Journal of Nuclear Medicine August 2022, 63 (supplement 2) 2801;
Jason Bini
1Yale University PET Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean-Dominique Gallezot
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Songye Li
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keunpoong Lim
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Emery
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Kapinos
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jim Ropchan
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nabeel Nabulsi
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ania Jastreboff
3Yale University School of Medicine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yiyun Huang
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Carson
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
Loading

Abstract

2801

Introduction: Cortisol is known to promote adipocyte differentiation and maturation, and prolonged exposure to excess cortisol contributes to development of obesity and metabolic dysregulation. The intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to active cortisol. Recently, we demonstrated reduced 11β-HSD1 levels in vivo in the human brain with increasing body mass index (BMI), while increasing brain 11β-HSD1 was seen with increasing age, using the PET radioligands [11C]- and [18F]AS2471907 (1). In addition to high uptake in the brain, [18F]AS2471907 has high uptake and specific binding in the liver (2). The amount of 11β-HSD1 in tissues such as liver and brain measured simultaneously by PET imaging may help elucidate the complex interplay of cortisol activation in the setting of metabolic dysregulation. With this in mind, we performed human PET imaging studies to examine 11β-HSD1 levels in the liver in addition to the brain.

Methods: Nine individuals (5F/4M, 29-64 y) with a range of BMIs (22.6 - 34.4 kg/m2) underwent PET/CT imaging with arterial sampling (n=7), after injection of [18F]AS2471907, by acquiring 18 x 5 min whole-body continuous bed motion images after a 10 min initial scan over the heart. Two acquisitions were centered over the liver for the duration of the scan. Regions-of-interest (ROI) for the liver were manually drawn on a summed PET image (60-90 min). Seventeen brain ROIs were selected from the anatomical automatic labeling (AAL) template and applied to the dynamic PET images to generate time-activity-curves (TACs). Volume of distribution (VT, mL/cm3) was estimated for each ROI using the multilinear analysis-1 (MA1) method with t*=10 min and tmax=90 min using the metabolite-corrected arterial plasma input function (IF). Mean whole-brain VT values were calculated by averaging all ROIs. Reversible 1- and 2-tissue compartment models, MA1, and the Logan graphical analysis, with the metabolite-corrected arterial plasma IF were applied to the liver TACs. Given the possibility of irreversible kinetics in the liver, Ki (min-1), the rate of irreversible tracer uptake, was calculated using the Patlak method. Liver SUV 60-90 min was also calculated.

Results: Uptake of [18F]AS2471907 in the brain and liver can be seen in a representative whole-body coronal slice (SUV 60 ‑ 90min) (Fig 1A). Liver TACs show varied uptake levels among lean, overweight, and obese subjects (Fig 1B). Mean ± SEM of the parent fraction in plasma was 88±1% at 90 min (n=7). Kinetic modeling demonstrated decreasing whole brain VT estimates with increasing BMI (R2=0.53; Fig 1C) and increasing VT with increasing age (R2=0.31; Fig 1D), similar to our previously published study examining only the brain in a larger cohort [1]. While TACs were fit well, none of the reversible models provided stable estimates for liver VT. Under the assumption of irreversible kinetics, the Patlak method provided good TAC fits and good Ki estimates. In contrast to the correlation of brain VT with BMI and age, liver Ki positively correlated with BMI (R2=0.57; Fig 1D) and negatively correlated with age (R2=0.49; Fig 1E).

Conclusions: These preliminary studies suggest obesity is associated with increased levels of 11β-HSD1 in the liver but decreased levels in the brain; while aging may increase brain 11β-HSD1 levels. One caveat is higher liver to brain 11β-HSD1 enzyme levels could make tracer kinetics in the liver look irreversible when in fact the kinetics may be very slow. Additional studies are needed to clarify this issue, and to ascertain the correlation of brain and liver 11β-HSD1 levels with obesity and its significance.

REFERENCES:

[1] Bini, et al, Molecular Imaging and Biology, 2020.

[2] Bini, et al, IEEE Trans on Radiation and Plasma Medical Sciences, 2021

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Previous
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 63, Issue supplement 2
August 1, 2022
  • Table of Contents
  • Index by author
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.
Liver and Brain Levels of 11β-hydroxysteroid Dehydrogenase Type 1 Enzyme in Obesity: Preliminary Results from PET Imaging Studies
(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
Liver and Brain Levels of 11β-hydroxysteroid Dehydrogenase Type 1 Enzyme in Obesity: Preliminary Results from PET Imaging Studies
Jason Bini, Jean-Dominique Gallezot, Songye Li, Keunpoong Lim, Paul Emery, Michael Kapinos, Jim Ropchan, Nabeel Nabulsi, Ania Jastreboff, Yiyun Huang, Richard Carson
Journal of Nuclear Medicine Aug 2022, 63 (supplement 2) 2801;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Liver and Brain Levels of 11β-hydroxysteroid Dehydrogenase Type 1 Enzyme in Obesity: Preliminary Results from PET Imaging Studies
Jason Bini, Jean-Dominique Gallezot, Songye Li, Keunpoong Lim, Paul Emery, Michael Kapinos, Jim Ropchan, Nabeel Nabulsi, Ania Jastreboff, Yiyun Huang, Richard Carson
Journal of Nuclear Medicine Aug 2022, 63 (supplement 2) 2801;
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics

Related Articles

  • No related articles found.
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Radioiodine therapy for Graves' hyperthyroidism with a large goiter
  • Indocyanine green fluorescence-guided parathyroidectomy. Our Experience.
Show more Non-oncology Endocrinology/Neuroendocrine

Similar Articles

SNMMI

© 2025 SNMMI

Powered by HighWire