抄録
Recently, much attention has been paid to "functional imaging", which observe biological functions rather than anatomical structures. Ultrasound imaging can be utilized for such functional imaging with appropriate biomolecular targeting contrast agents. One of limitations of currently available contrast agents for ultrasound is that they are microbubbles with diameter of several micrometers and can only be applicable to targets inside blood vessels. To target other tissues than those in blood vessels, much smaller contrast agents are needed. As an approach to obtain such agents, we have been studying contrast agents utilizing nano-sized phase-shift colloids. The concept is that liquid-containing colloidal particles less than 200 nm are administrated in living body and then the liquid changes its phase to gas by external stimuli such as ultrasound. We obtained micelles containing phospholipids and volatile perfluorocarbon(PFC)s including Perfluoro-n-pentane (n-PFP, b.p. 29 ℃) and 2H,3H-Perfluoropentane (DFP, b.p. 53.6 ℃) by high-pressure emulsification and investigated their properties in vitro. The micelles were put into a tube with diameter of 2 mm and exposed focused ultrasound at 3.4 MHz while monitoring with a diagnostic ultrasound scanner (EUB-8500, Hitachi Medical Corp.). Microbubble generation was observed only at the focus of the ultrasound. When the micelle with the mixtures of n-PFP and DFP were used, it was found that acoustic intensity thresholds for microbubble formation increased as the ratio of DFP to n-PFP which suggests that, by changing the ratio of the two material, required ultrasound energy for microbubble formation can be controlled. Our results indicate a new type of contrast agent featuring controllable in situ phase shift of liquid to gas. Part of this work was supported by Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.
