An In Vivo Evaluation of the Effect of Repeated Administration and Clearance of Targeted Contrast Agents on Molecular Imaging Signal Enhancement

Competitive inhibition diminishes ligand adhesion as receptor sites become occupied with competing ligands. It is unknown if this effect occurs in ultrasound molecular imaging studies where endothelial binding sites become occupied with adherent bubbles or bubble fragments. The goal of this pilot study was to assess the effect that repeated administration and clearance of targeted agents has on successive adhesion. Two groups of animals were imaged with 3-D ultrasonic molecular imaging. Injections and imaging were performed on Group 1 at time 0 and 60 minutes. Group 2 received injections of microbubbles at 0, 15, 30, 45 and 60 minutes with imaging at 0 and 60 minutes. At 60 minutes, Group 1 targeting relative to baseline was not significantly different from Group 2 (1.06±0.27 vs. 1.08±0.34, p=0.93). Data suggest that multiple injections of targeted microbubbles do not block sufficient binding sites to bias molecular imaging data in serial studies.