Macrophage ablation significantly reduces uptake of imaging probe into organs of the reticuloendothelial system

Abstract

Background Macrophages engulf particulate contrast media, which is pivotal for biomedical imaging. Purpose To introduce a macrophage ablation animal model by showing its power to manipulate the kinetics of imaging probes. Material and Methods The kinetics of a particulate computed tomography (CT) contrast media was compared in macrophage ablative mice and normal mice. Liposomes (size 220 µg), loaded with clodronate, were injected into the peritoneum of three C57BL/6 mice. On the third day, 200 µL of the particulate agent ExiTron nano 6000 were injected into three macrophage-ablative mice and three control mice. CT scans were acquired before and 3 min, 1 h, 6 h, and 24 h after the ExiTron application. The animals were sacrificed, and their spleens and livers removed. Relative CT values (CTV) were measured and analyzed. Results Liver and spleen enhancement of treated mice and controls were increasing over time. The median peak values were different with 225 CTV for treated mice and 582 CTV for controls in the liver ( P = 0.032) and 431 CTV for treated and 974 CTV in controls in the spleen ( P = 0.016). Conclusion Macrophage ablation leads to a decrease of enhancement in organs containing high numbers of macrophages, but only marginal changes in macrophage-poor organs. Macrophage ablation can influence the phagocytic activity and thus opens new potentials to investigate and manipulate the uptake of imaging probes.