Vascular immunotargeting to endothelial surface in a specific macrodomain in alveolar capillaries

A novel 85 kD glycoprotein (gp85) is a marker of the avesicular zone, a thi n part of pulmonary endothelial cells separating alveolar and vascular comp artments and lacking vesicles. This report presents the first evaluation wh ether mAb 30B3, a monoclonal antibody to gp85, can be used for targeting of drugs to the surface of lung endothelium. I-125-mAb 30B3 accumulated in is olated perfused lungs (IPL) (22.8 +/- 1.1 versus 0.5 +/- 0.1 %ID/g for I-12 5-IgG) and accumulated preferentially in the lungs after intravenous or int raarterial injection (10.9 +/- 0.7 and 11.0 +/- 1.5 versus 0.9 +/- 0.2 %ID/ g for I-125-IgG). I-125-mAb 30B3 uptake in IPL was rapid (T1/2 15 min), sat urable (B-max appr. 10(5) molecules/cell), specific (inhibited by nonlabele d mAb 30B3) and temperature independent (26.3 +/- 2.1 versus 22.8 +/- 1.1 % ID/g at 6 degrees C versus 37 degrees C). Biotinylated mAb 30B3 permitted s ubsequent accumulation of perfused avidin derivative in IPL. Because these data indicated that mAb 30B3 binds to an accessible, poorly internalizable antigen in the lung, we conjugated mAb 30B3 with a plasminogen activator, I -125-tPA. After intravenous injection in rats, lung-to-blood ratio was 8.4 +/- 0.9 for mAb 30B3/I-125-tPA versus 0.4 +/- 0.1 for IgG/I-125-tPA, indica ting that mAb 30B3 may deliver drugs, which was supposed to exert therapeut ic action in the vascular lumen (e.g., antithrombotic proteins), to the sur face of pulmonary endothelium.