Magnetic resonance in medicine · 2025
Trityl OXO71 Pharmacokinetics and Distribution in Rhesus Macaques.
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Kroenke Christopher D, Canavesi Irene, Castro Jenna N, Karpf Joshua A, Khurana Raman, Holloway Megan M, Palha Mitasha S, Legenzov Eric A, Crilly Nathan P, Epel Boris, Driesschaert Benoit, Rawal Viresh H, Kao Joseph P Y, Buehler Paul W, Roberts Victoria H J, Kotecha Mrignayani
Аннотация
PURPOSE: Electron paramagnetic resonance oxygen imaging (EPROI) techniques have the ability to quantify the partial pressure of oxygen (pO2), in vivo, through quantitative measurement of T1e maps of the trityl radical, OXO71. OXO71-based EPROI has seen several applications in small animal imaging studies, but translation to humans will benefit from optimization of EPROI using large animal subjects that are anatomically and physiologically similar to humans. The goal of this study was to characterize pharmacokinetics and tissue distribution following an intravenous administration of OXO71 in rhesus macaques.
METHODS: A 92 μmol/kg OXO71 dose, equivalent to doses used in studies with other animal species, was administered as a bolus injection over a 10-min period in 3 animals. Plasma and urine were sampled over the subsequent 2 h. A second equivalent dose was then rapidly administered, animals were euthanized, and OXO71 distribution was assessed in harvested tissues by EPR imaging.
RESULTS: Pharmacokinetics of plasma OXO71 determined by EPR spectroscopy showed biphasic clearance, characterized by distinct initial and terminal half-lives of 12.4 ± 1.2 min and 67.7 ± 8.9 min, respectively. Some variability in trityl concentration was observed between organs, but appreciable concentration was found for all tissues except the brain.
CONCLUSION: No adverse physiological effects of the infusions were observed, consistent with a low toxicity of OXO71. These findings indicate EPROI using OXO71 is safe in primates, and provide information related to the dose and time constraints for performing EPROI in other large animal species including humans.
METHODS: A 92 μmol/kg OXO71 dose, equivalent to doses used in studies with other animal species, was administered as a bolus injection over a 10-min period in 3 animals. Plasma and urine were sampled over the subsequent 2 h. A second equivalent dose was then rapidly administered, animals were euthanized, and OXO71 distribution was assessed in harvested tissues by EPR imaging.
RESULTS: Pharmacokinetics of plasma OXO71 determined by EPR spectroscopy showed biphasic clearance, characterized by distinct initial and terminal half-lives of 12.4 ± 1.2 min and 67.7 ± 8.9 min, respectively. Some variability in trityl concentration was observed between organs, but appreciable concentration was found for all tissues except the brain.
CONCLUSION: No adverse physiological effects of the infusions were observed, consistent with a low toxicity of OXO71. These findings indicate EPROI using OXO71 is safe in primates, and provide information related to the dose and time constraints for performing EPROI in other large animal species including humans.