Dose-dependent safety and renal ultrasound contrast kinetics of oxygen microbubbles in healthy dogs

Oxygen microbubbles (OMB) are lipid-shelled ultrasound contrast agents with an oxygen gas core that show promise as theranostic agents for diagnostic imaging and enhancing radiotherapy efficacy in preclinical rodent models. By improving oxygenation in hypoxic tumor regions, OMBs may increase radiosensitivity. However, their safety, tolerability, and potential to act as vascular imaging contrast agents have yet to be assessed in larger animals. In this study, four healthy beagle dogs received intravenous OMBs at escalating doses 1, 10, and 100 μl/kg at 1-week intervals. Over a 4-week observation period, key physiological parameters, including temperature, pulse, and respiration, were monitored alongside complete blood counts, blood biochemistry, coagulation panels, and urinalysis. Additionally, the ability of OMBs to enhance contrast during kidney ultrasound imaging was evaluated, and pharmacokinetic parameters were estimated. Across all doses, OMB administration was well tolerated, with no clinically significant changes in vital signs or laboratory values. Ultrasound imaging revealed dose-dependent increases in renal contrast enhancement. Pharmacokinetic analyses confirmed that higher doses prolonged contrast enhancement and improved image quality. This study provides an initial safety and diagnostic benchmark for OMB administration in dogs, laying the groundwork for future investigations into their theranostic potential.