IN-VIVO IMAGING OF INFLAMMATION USING AN APTAMER INHIBITOR OF HUMAN NEUTROPHIL ELASTASE

Background: We previously reported the isolation of aptamer irreversib le inhibitors of human neutrophil elastase. We now report on the appli cation of aptamer technology to the field of diagnostic imaging. Resul ts: The enzyme elastase has been reported to bind to the surface of ac tivated neutrophils. Using a fluorescent flow cytometry assay, we show ed that an aptamer inhibitor of elastase also binds preferentially to activated neutrophils. We then tested the ability of the aptamer to im age inflammation in vivo in a rat reverse passive Arthus reaction mode l. The aptamer achieved a peak target-to-background (T/B) ratio of 4.3 +/- 0.6 in 2 hours. IgG, which is used clinically to image inflammati on, took a longer time to achieve a lower T/B: 3.1 +/- 0.1 at 3 hours. The difference in T/B values is due. to the faster clearance of the a ptamer signal from the blood pool. Conclusions: It is feasible to appl y aptamer ligands for use in diagnostic imaging, where they may offer significant advantages over monoclonal antibodies and other reagents.