Early detection of oleic acid-induced lung injury in rats using (111)In-labeled anti-rat intercellular adhesion molecule-1

Previous study of the bleomycin-induced lung injury model suggested that (111)In-labeled antirat intercellular adhesion molecule-1 (aICAM-1) might be a useful acute respiratory distress syndrome (ARDS) diagnostic agent. We further investigated the ability of (111)In-aICAM-1 to detect inflammation in another ARDS lung injury model. (111)In-labeled rat polymorphonuclear leukocytes (PMNs), (111)In-aICAM-1, (111)In-labeled normal mouse IgG (nmIgG), and (111)In-labeled rat serum albumin (RSA) were injected into rats 18-24 h before kill. Biodistributions, scintigraphic images, and lung ICAM-1 upregulation were obtained in uninjured rats and in rats after injury with oleic acid. (111)In-RSA and (111)In-nmIgG localized in inflamed lung at 5 min postinjury (PI). (111)In-PMN uptake increased significantly only at 24 h PI. (111)In-aICAM-1 localization increased significantly (30%-60%) at 1 h PI and remained elevated up to 24 h PI. Lung/blood ratios (L/B) at 1 and 4 h PI were very low (1 and 25%-60% higher than those for the control samples. A low L/B suggests poor inflammation detection on the images. Images and region-of-interest analysis confirmed that only (111)In-aICAM-1 could distinguish inflamed lungs at 4 h PI. ICAM-1 was upregulated at 4 and 24 h PI. In this model, (111)In-aICAM-1 detected lung inflammation very early in the course of the disease. These results support the suggestion that (111)In-aICAM-1 could be a very early, highly specific ARDS diagnostic agent and may be useful to detect a wide range of inflammations.