RT Journal Article
SR Electronic
T1 [<sup>11</sup>C]PS13 Demonstrates Pharmacologically Selective and Substantial Binding to Cyclooxygenase-1 in the Human Brain
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 117
OP 122
DO 10.2967/jnumed.124.267928
VO 66
IS 1
A1 Ghazanfari, Nafiseh
A1 Liow, Jeih-San
A1 Kim, Min-Jeong
A1 Cureton, Raven
A1 Lee, Adrian
A1 Knoer, Carson
A1 Jenkins, Madeline
A1 Hong, Jinsoo
A1 Santamaria, Jose A. Montero
A1 Shetty, H. Umesha
A1 Galassi, Anthony
A1 Wighton, Paul
A1 Nørgaard, Martin
A1 Greve, Douglas N.
A1 Zoghbi, Sami S.
A1 Pike, Victor W.
A1 Innis, Robert B.
A1 Zanotti-Fregonara, Paolo
YR 2025
UL http://jnm.snmjournals.org/content/66/1/117.abstract
AB 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.