J Charlton1, J Sennello, D Smith. 1. NeXstar Pharmaceuticals, Inc., 2860 Wilderness Place, Boulder, CO 80301, USA.
Abstract
BACKGROUND: We previously reported the isolation of aptamer irreversible inhibitors of human neutrophil elastase. We now report on the application of aptamer technology to the field of diagnostic imaging. RESULTS: The enzyme elastase has been reported to bind to the surface of activated neutrophils. Using a fluorescent flow cytometry assay, we showed that an aptamer inhibitor of elastase also binds preferentially to activated neutrophils. We then tested the ability of the aptamer to image inflammation in vivo in a rat reverse passive Arthus reaction model. 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 inflammation, 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 aptamer signal from the blood pool. CONCLUSIONS: It is feasible to apply aptamer ligands for use in diagnostic imaging, where they may offer significant advantages over monoclonal antibodies and other reagents.
BACKGROUND: We previously reported the isolation of aptamer irreversible inhibitors of humanneutrophil elastase. We now report on the application of aptamer technology to the field of diagnostic imaging. RESULTS: The enzyme elastase has been reported to bind to the surface of activated neutrophils. Using a fluorescent flow cytometry assay, we showed that an aptamer inhibitor of elastase also binds preferentially to activated neutrophils. We then tested the ability of the aptamer to image inflammation in vivo in a rat reverse passive Arthus reaction model. 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 inflammation, 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 aptamer signal from the blood pool. CONCLUSIONS: It is feasible to apply aptamer ligands for use in diagnostic imaging, where they may offer significant advantages over monoclonal antibodies and other reagents.