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Early Detection of Oleic Acid-Induced Lung Injury in Rats Using ¹¹¹In-Labeled Anti-Rat Intercellular Adhesion Molecule-1

Departments of Diagnostic Imaging and Therapeutics, Medicine, Surgery, and Pharmacology, University of Connecticut Health Center, Farmington; and Department of Radiology, VA Medical Center, Newington, Connecticut

Previous study of the bleomycin-induced lung injury model suggested that ¹¹¹In-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 ¹¹¹In-aICAM-1 to detect inflammation in another ARDS lung injury model. Methods: ¹¹¹In-labeled rat polymorphonuclear leukocytes (PMNs), ¹¹¹In-aICAM-1, ¹¹¹In-labeled normal mouse IgG (nmIgG), and ¹¹¹In-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. Results: ¹¹¹In-RSA and ¹¹¹In-nmIgG localized in inflamed lung at 5 min postinjury (PI). ¹¹¹In-PMN uptake increased significantly only at 24 h PI. ¹¹¹In-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 (<0.6) for ¹¹¹In-nmIgG and ¹¹¹In-PMN rats; however, for ¹¹¹In-aICAM-1 rats, they were >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 ¹¹¹In-aICAM-1 could distinguish inflamed lungs at 4 h PI. ICAM-1 was upregulated at 4 and 24 h PI. Conclusion: In this model, ¹¹¹In-aICAM-1 detected lung inflammation very early in the course of the disease. These results support the suggestion that ¹¹¹In-aICAM-1 could be a very early, highly specific ARDS diagnostic agent and may be useful to detect a wide range of inflammations.

Key Words: inflammation • acute respiratory distress syndrome • adhesion molecules • inflammation imaging • immunoscintigraphy

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