Accelerated clearance of ultrasound contrast agents containing polyethylene glycol (PEG) is associated with a PEG-specific immune response

Lipid-shelled microbubbles (MBs) are routinely used as contrast agents for ultrasound imaging. Such MBs are often formulated with polyethylene glycol (PEG), with the intention of shielding them from recognition and clearance by the innate immune system, prolonging their intravenous circulation time. Paradoxically, the immune system is able to generate specific antibodies that bind PEG. This has been associated with accelerated blood clearance of PEGylated particles when dosed repeatedly over multiple days. Here we aim to (1) study how PEGylated MB pharmacokinetics changes during repeat contrast-enhanced ultrasound imaging schedules and (2) investigate whether administration of these MBs generates an anti-PEG antibody response in rats.