Effect of Microbubble-enhanced Ultrasound on Prostate Permeability: A Potential Therapeutic Method for Prostate Disease

OBJECTIVE To explore the effect of microbubble-enhanced therapeutic ultrasound (MEUS) on prostate permeability and the blood-prostate barrier. METHODS Experimental rabbits were assigned to 5 separate groups; the MEUS group, the MEUS 24-hour group, and the 3 control groups. A therapeutic ultrasound device was used to treat the rabbit prostates in vivo in combination with intravenous injection of microbubbles (MBs). Evans blue (EB) and lanthanum (La) nitrate were injected to assess the prostate permeability using laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). RESULTS The MEUS group exhibited a significant increase in EB exudation and EB staining of the glandular parenchyma compared with the control groups. In the MEUS group, LSCM showed that a bright red fluorescence of EB was extensively distributed in the intercellular space of extravascular stroma and the glandular epithelium. In addition, TEM showed that the tight junction between vascular endothelial cells was opened, and the La particles used as tracers were seen in the stroma and glandular epithelium. The alterations in the MEUS group were significantly different from those in the groups exposed to MBs or ultrasound alone. These alterations were also not observed in the MEUS 24-hour group. CONCLUSION MEUS enhanced the prostate permeability, and it effectively opened the blood-prostate barrier. Hence, MEUS may serve as a potential noninvasive therapy for targeted drug or gene delivery to the prostate. However, the relationship between the acoustic parameters of MEUS and prostate permeability or the bioeffects of MEUS needs to be evaluated in future studies. UROLOGY 81: 921.e1-921.e7, 2013. (C) 2013 Elsevier Inc.