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Research ArticleClinical Investigation

[11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain

Nafiseh Ghazanfari, Jeih-San Liow, Min-Jeong Kim, Raven Cureton, Adrian Lee, Carson Knoer, Madeline Jenkins, Jinsoo Hong, Jose A. Montero Santamaria, H. Umesha Shetty, Anthony Galassi, Paul Wighton, Martin Nørgaard, Douglas N. Greve, Sami S. Zoghbi, Victor W. Pike, Robert B. Innis and Paolo Zanotti-Fregonara
Journal of Nuclear Medicine January 2025, 66 (1) 117-122; DOI: https://doi.org/10.2967/jnumed.124.267928
Nafiseh Ghazanfari
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Jeih-San Liow
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Min-Jeong Kim
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
2Stony Brook University School of Medicine, Stony Brook, New York;
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Raven Cureton
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Adrian Lee
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Carson Knoer
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Madeline Jenkins
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Jinsoo Hong
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Jose A. Montero Santamaria
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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H. Umesha Shetty
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Anthony Galassi
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Paul Wighton
3Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts; and
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Martin Nørgaard
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
4University of Copenhagen, Copenhagen, Denmark
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Douglas N. Greve
3Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts; and
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Sami S. Zoghbi
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Victor W. Pike
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Robert B. Innis
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Paolo Zanotti-Fregonara
1Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland;
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Abstract

Our laboratory recently developed [11C]PS13 as a PET radioligand to selectively measure cyclooxygenase-1 (COX-1). The cyclooxygenase enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [11C]PS13, which is composed of both specific binding and background uptake, can be accurately quantified with gold standard methods of compartmental modeling. This study sought to quantify the specific binding of [11C]PS13 to COX-1 in healthy human brain using scans performed with arterial input function at baseline and after blockade by the COX-1–selective inhibitor ketoprofen. Methods: Eight healthy volunteers underwent two 90-min [11C]PS13 PET scans with radiometabolite-corrected arterial input function, at baseline and about 2 h after oral administration of ketoprofen (75 mg). Results: Two-tissue compartment modeling effectively identified the total uptake of radioactivity in the brain (as distribution volume), showing the highest densities in the hippocampus, the occipital cortex, and the banks of the central sulcus. All brain regions exhibited displaceable and specific binding, and thus none could be used as a reference region. Ketoprofen blocked approximately 84% of the binding sites on COX-1 in the whole brain. After full occupancy was extrapolated, the average whole-brain values of [11C]PS13 were 1.6 ± 0.8 mL·cm−3 for specific uptake, 1.7 ± 0.6 mL·cm−3 for background uptake, and 1.1 ± 0.5 for the specific-to-background ratio. The hippocampus had the highest specific-to-background ratio value of 2.7 ± 0.9. Conclusion: [11C]PS13 exhibited high specific binding to COX-1 in the human brain, but its quantification requires arterial blood sampling.

  • [11C]PS13
  • COX-1
  • brain
  • human
  • occupancy

Footnotes

  • Published online Nov. 14, 2024.

  • © 2025 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 66 (1)
Journal of Nuclear Medicine
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January 1, 2025
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[11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain
Nafiseh Ghazanfari, Jeih-San Liow, Min-Jeong Kim, Raven Cureton, Adrian Lee, Carson Knoer, Madeline Jenkins, Jinsoo Hong, Jose A. Montero Santamaria, H. Umesha Shetty, Anthony Galassi, Paul Wighton, Martin Nørgaard, Douglas N. Greve, Sami S. Zoghbi, Victor W. Pike, Robert B. Innis, Paolo Zanotti-Fregonara
Journal of Nuclear Medicine Jan 2025, 66 (1) 117-122; DOI: 10.2967/jnumed.124.267928

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[11C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain
Nafiseh Ghazanfari, Jeih-San Liow, Min-Jeong Kim, Raven Cureton, Adrian Lee, Carson Knoer, Madeline Jenkins, Jinsoo Hong, Jose A. Montero Santamaria, H. Umesha Shetty, Anthony Galassi, Paul Wighton, Martin Nørgaard, Douglas N. Greve, Sami S. Zoghbi, Victor W. Pike, Robert B. Innis, Paolo Zanotti-Fregonara
Journal of Nuclear Medicine Jan 2025, 66 (1) 117-122; DOI: 10.2967/jnumed.124.267928
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Keywords

  • [11C]PS13
  • COX-1
  • brain
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  • occupancy
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