Biodistributions of air-filled albumin microspheres in rats and pigs

Abstract

The air-filled microspheres of the ultrasound-contrast agent Albunex are unique in that the walls consist of human serum albumin molecules which have been made insoluble by sonication of the albumin solution. The microspheres were isolated by flotation, and the washed microspheres were labelled with 125I. The labelled material was cleared from the circulation mainly as particles, not as soluble albumin molecules. In rats, 80% of intravenously injected microspheres were cleared from the blood within 2 min. Nearly 60% of the dose was recovered in the liver, only 5% in the lungs, 9% in the spleen, and negligible quantities in kidneys, heart and brain. Of the radioactivity in the liver, more than 90% was taken up by Kupffer cells (liver macrophages). The protein in the liver was degraded apparently with first-order kinetics (half-life 40 min). In pigs, over 90% of the intravenously injected dose was recovered in the lungs. The vastly increased recovery in pig lungs, compared with that in rats, is probably due to the pulmonary intravascular macrophages of the pig; macrophages are not normally found in this location in rats (or humans). In a separate series of experiments in rats, the biodistribution of shell material from the microspheres was examined. The microspheres were made to collapse by applying external pressure on the suspension, leaving sedimentable protein material consisting of layers of insoluble albumin from the 'shells' surrounding the air bubble. The 'shells' and the microspheres were cleared from the circulation and taken up by the liver with the same kinetics. In the lungs, a higher proportion (15%) of shells than of microspheres was recovered.

Targeted Microbubbles for Imaging Tumor Angiogenesis: Assessment of Whole-Body Biodistribution with Dynamic Micro-PET in Mice

“…In the liver, targeted MBs were found in Kupffer cells as early as 4 minutes after administration. This finding is consistent with that in a study by Walday et al (10).…”

“…Walday et al (10) used traditional ex vivo biodistribution techniques to study the organ distribution of first-generation, nontargeted air-filled iodine 125-labeled albumin microspheres (Albunex) in both rats and pigs up to 90 minutes after intravenous administration. Three minutes after administration in rats, about 60% of the radiolabeled albumin microspheres were recovered in the liver, 9% of them were recovered in the spleen, and 5% of them were recovered in the lungs, with only small amounts in other organs such as the brain, heart, and kidneys (10). In contrast, in pigs, more than 90% of the albumin microspheres were recovered in the lungs, most likely because of the presence of intravascular macrophages in the porcine lungs (10).…”

“…Three minutes after administration in rats, about 60% of the radiolabeled albumin microspheres were recovered in the liver, 9% of them were recovered in the spleen, and 5% of them were recovered in the lungs, with only small amounts in other organs such as the brain, heart, and kidneys (10). In contrast, in pigs, more than 90% of the albumin microspheres were recovered in the lungs, most likely because of the presence of intravascular macrophages in the porcine lungs (10). In another study, the biodistribution of air-filled iodine 123-labeled human serum albumin microspheres (Quantison) was studied in humans for 58 hours by using scintigraphic imaging (9).…”

“…Researchers in two studies (9,10) have evaluated biodistribution of nontargeted MBs in rats, pigs, and humans. To our knowledge, biodistribution of targeted MBs in living animals by using positron emission tomography (PET) has not been studied to date.…”

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

“…We observed that the volume of ethanol can be substantially reduced to 0.8 mL (compared with 40 mL, as published previously [22,23]), which caused moderate-to-severe TNBS-mediated inflammation with minimal discomfort to the animals. Another detail worth noting is the need to premedicate pigs with aspirin, indomethacin, or a specific thromboxane receptor blocker before injecting lipid-based particles such as MBs (16)(17)(18), because pigs have abundant intrapulmonary macrophages (26,27). These macrophages rapidly clear intravenously injected particles and immediately release substances such as vasoconstrictor thromboxane A2, with subsequent pulmonary arterial hypertension, systemic…”