Skip to main content

Main menu

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

Quantification of macrophage-driven inflammation during myocardial infarction with 18F-LW223, a novel TSPO radiotracer with binding independent of the rs6971 human polymorphism

Mark G. MacAskill, Agne Stadulyte, Lewis Williams, Timaeus E. F. Morgan, Nikki L. Sloan, Carlos J. Alcaide-Corral, Tashfeen Walton, Catriona Wimberley, Chris-Anne McKenzie, Nick B. Spath, William Mungall, Ralph BouHaidar, Marc R. Dweck, Gillian A. Gray, David E. Newby, Christophe Lucatelli, Andrew Sutherland, Sally Pimlott and Adriana A. S. Tavares
Journal of Nuclear Medicine August 2020, jnumed.120.243600; DOI: https://doi.org/10.2967/jnumed.120.243600
Mark G. MacAskill
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mark G. MacAskill
Agne Stadulyte
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lewis Williams
2 University of Glasgow;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timaeus E. F. Morgan
2 University of Glasgow;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nikki L. Sloan
2 University of Glasgow;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos J. Alcaide-Corral
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tashfeen Walton
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Catriona Wimberley
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chris-Anne McKenzie
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nick B. Spath
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William Mungall
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ralph BouHaidar
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc R. Dweck
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gillian A. Gray
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David E. Newby
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christophe Lucatelli
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Sutherland
2 University of Glasgow;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sally Pimlott
3 Greater Glasgow and Clyde NHS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adriana A. S. Tavares
1 University of Edinburgh, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Supplemental
  • Info & Metrics
  • PDF
Loading

Abstract

Rationale: Myocardial infarction (MI) is one of the leading causes of death worldwide and inflammation is central to the tissue response and patient outcomes. The 18kDa translocator protein (TSPO) has been utilized in positron emission tomography (PET) as an inflammatory biomarker. The aims of this study were to: 1) screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart, 2) assess whether the in vivo characteristics of our lead radiotracer, 18F-LW223, are suitable for clinical translation and 3) validate whether 18F-LW223 can detect macrophage driven inflammation in a rat myocardial infarction model. Methods: Fifty-one human brain and twenty-nine human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3H-PK11195 and the following ligands: PK11195, PBR28 and our novel compounds (AB5186 and LW223). Naive rats and mice were used for in vivo PET kinetic studies, radiometabolite studies and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with invasive input function at 7 days following MI. For quantification of PET signal in the hypoperfused myocardium, K1 was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BPTC). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (62% of parent at 120 min), a high plasma free fraction of 38.5% and a suitable dosimetry profile (effective dose of 20.5-24.5 μSv/MBq). 18F-LW223 BPTC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of naive animals (36.9±8.8 vs. 10.0±2.4 cm3/ml/min, p≤0.001). Ex-vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BPTC analysis. Conclusion: 18F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics and is able to accurately map macrophage driven inflammation following MI.

  • Animal Imaging
  • Cardiology (basic/technical)
  • Cardiology (clinical)
  • Molecular Imaging
  • PET/CT
  • Radiochemistry
  • Inflammation
  • Macrophage
  • Myocardial Infarction
  • PET
  • TSPO
  • Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine: 62 (4)
Journal of Nuclear Medicine
Vol. 62, Issue 4
April 1, 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
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.
Quantification of macrophage-driven inflammation during myocardial infarction with 18F-LW223, a novel TSPO radiotracer with binding independent of the rs6971 human polymorphism
(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
Quantification of macrophage-driven inflammation during myocardial infarction with 18F-LW223, a novel TSPO radiotracer with binding independent of the rs6971 human polymorphism
Mark G. MacAskill, Agne Stadulyte, Lewis Williams, Timaeus E. F. Morgan, Nikki L. Sloan, Carlos J. Alcaide-Corral, Tashfeen Walton, Catriona Wimberley, Chris-Anne McKenzie, Nick B. Spath, William Mungall, Ralph BouHaidar, Marc R. Dweck, Gillian A. Gray, David E. Newby, Christophe Lucatelli, Andrew Sutherland, Sally Pimlott, Adriana A. S. Tavares
Journal of Nuclear Medicine Aug 2020, jnumed.120.243600; DOI: 10.2967/jnumed.120.243600

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Quantification of macrophage-driven inflammation during myocardial infarction with 18F-LW223, a novel TSPO radiotracer with binding independent of the rs6971 human polymorphism
Mark G. MacAskill, Agne Stadulyte, Lewis Williams, Timaeus E. F. Morgan, Nikki L. Sloan, Carlos J. Alcaide-Corral, Tashfeen Walton, Catriona Wimberley, Chris-Anne McKenzie, Nick B. Spath, William Mungall, Ralph BouHaidar, Marc R. Dweck, Gillian A. Gray, David E. Newby, Christophe Lucatelli, Andrew Sutherland, Sally Pimlott, Adriana A. S. Tavares
Journal of Nuclear Medicine Aug 2020, jnumed.120.243600; DOI: 10.2967/jnumed.120.243600
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Figures & Data
  • Supplemental
  • Info & Metrics
  • PDF

Related Articles

  • This Month in JNM
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Keywords

  • Animal Imaging
  • Cardiology (basic/technical)
  • Cardiology (clinical)
  • Molecular Imaging
  • PET/CT
  • Radiochemistry
  • Inflammation
  • macrophage
  • myocardial infarction
  • PET
  • TSPO
SNMMI

© 2021 Journal of Nuclear Medicine

Powered by HighWire