Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium

Background-The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hy pothesis that albumin-coated microbubbles could be used to effectively deli ver an adenoviral transgene to rat myocardium by ultrasound-mediated microb ubble destruction, Methods and Results-Recombinant adenovirus containing beta-galactosidase an d driven by a constitutive promoter was attached to the surface of albumin- coated, perfluoropropane-filled microbubbles, These bubbles were infused in to the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contai n virus, virus alone, and virus plus ultrasound. One group underwent ultras ound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for beta-galactosidase expressio n. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chlor o-3-indolyl-beta-D-galactopyranoside substrate, indicating expression of th e transgene. None of the control animals showed myocardial expression of th e beta-galactosidase transgene. By quantitative analysis, beta-galactosidas e activity was 10-fold higher in the treated group than in controls (P<0.00 01). Conclusions-Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.