Interaction of diagnostic ultrasound with synthetic oligonucleotide- labeled perfluorocarbon-exposed sonicated dextrose albumin microbubbles

The purpose of this study was to determine, first, whether the albumin on perfluorocarbon-exposed sonicated dextrose albumin microbubbles has retained its known ability to bind antisense oligonucleotides (DNA utilized to inhibit viral replication and intimal hyperplasia). The binding kinetics of synthetic antisense oligonucleotides to perfluorocarbon-exposed sonicated dextrose albumin microbubbles as well as to room air-containing sonicated dextrose albumin microbubbles were compared. Second, the effect of diagnostic ultrasound on this binding is unknown. The ability of diagnostic ultrasound to release synthetic antisense oligonucleotides from perfluorocarbon-exposed sonicated dextrose albumin microbubbles also was tested in vitro and in vivo in three dogs. Synthetic antisense oligonucleotides exhibited binding to perfluorocarbon-exposed sonicated dextrose albumin microbubbles much like that of native albumin but did not bind uniformly with room air-containing sonicated dextrose albumin microbubbles. Diagnostic ultrasound resulted in significant partitioning of synthetic antisense oligonucleotides into non- bubble containing regions after insonation in vitro as well as deposition of greater amounts of synthetic antisense oligonucleotides in the insonated kidney after intravenous injections of synthetic antisense oligonucleotide- labeled perfluorocarbon-exposed sonicated dextrose albumin microbubbles. We conclude that perfluorocarbon-exposed sonicated dextrose albumin microbubbles, unlike room air-containing sonicated dextrose albumin microbubbles, have bioactive albumin on their surface that can bind synthetic antisense oligonucleotides and then release them in the presence of diagnostic ultrasound.