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.