EARLY DETECTION OF BLEOMYCIN-INDUCED LUNG INJURY IN RAT USING INDIUM-111-LABELED ANTIBODY-DIRECTED AGAINST INTERCELLULAR-ADHESION MOLECULE-1

We have investigated whether an In-111-labeled mouse monoclonal antibo dy to rat intercellular adhesion molecule-1 (In-111aICAM-1) could det ect lung injury early in rats treated with bleomycin. Methods: Rats re ceived an intravenous injection of either In-111aICAM-1 or In-111-lab eled normal mouse IgG (In-111nmlgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomy cin 4 or 24 hr before the rats were killed. After death, tissue was re moved and activity was measured, lungs were cryostat-sectioned to dete ct the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-la was examined on blood polymorphonuclear leukocytes (PMNs) u sing fluorescence-activated cell-sorter (FAGS) analysis. Results: In r ats injected with In-111aICAM-1, the percent injected dose/organ in l ungs both at 4 and 24 hr postbleomycin increased significantly compare d to the values in either uninjured rats or rats that received In-111 nmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For In-111nmlgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1at 24 hr. In In-111aICAM-1 rats injured at 4 or 24 hr , images could easily be distinguished from uninjured rats, All images of In-111nmlgG rats showed only cardiac blood-pool and liver activit y with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs . Expression of LFA-1 alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values, Conclusio n: Biodistribution and imaging data demonstrate that In-111aICAM-1 ca n detect early acute bleomycin-induced lung injury. Immunofluorescence and FAGS data suggest that In-111ICAM-1 uptake is a specific process . This antibody has potential as an early radionuclide detector of acu te inflammations.