Preparation And Imaging Study Of Lipid Perfluorooctylbromide Nanoparticles

PART I EXPERIMENTAL STUDY ON PREPARATION AND CONTRAST ENHANCED COMPUTED TOMOGRAPHY EFFECT OF LIPID PERFLUOROOCTYLBROMIDE NANOPARTICLESObjective: To prepare lipid perfluorooctylbromide nanoparticles and to evaluate the effect of contrast enhanced computed tomography(CECT)in rats.Methods: Lipid perfluorooctylbromide nanoparticles were prepared by microfluidization techniques. The morpholog and distribution were observed with optical microscope. Particle size and Zeta potential were determined with laser light scattering analyzer. Twelve normal Wistar rats were performed directly contrast imaging after injection of perfluorooctylbromide nanoparticles via caudal vein. Vital signs of rats were monitored during the whole study. CT values in region of interest(ROI)were measured and the time-density curve(TDC)was drawn. Results: The size and distribution of nanoparticles were highly uniformed. Perfluorooctylbromide nanoparticles could produce density enhancement of great vessels, liver and spleen after intravenous injection. Significant differences of CT values in ROI between pre-contrast and post-contrast were observed(P< 0.05). Splenic enhancement was more significant and the duration was longer. No death or abnormal behaviors of rats were observed more than 4 weeks.Conclusion: This novel and safe lipid perfluorooctylbromide nanoparticles could make prolonged enhancement of rat's great vessels, liver and spleen, which has a good potential for CT imaging application.PART II IN VIVO EXPERIMENTAL STUDY ON CONTRAST ENHANCED UTRASOUND EFFECT OF LIPID PERFLUOROOCTYLBROMIDE NANOPARTICLESObjective: To prepare a kind of new lipid perfluorooctylbromide nanoparticles and to explore its potential application as an ultrasound contrast agent(UCA)of liver. Methods: The morpholog and distribution of lipid perfluorooctylbromide nanoparticles were observed with optical microscope and transmission electron microscope(TEM). Twelve normal Wistar rats were performed directly contrast imaging with a 10 MHz linear-array transducer after injection of perfluorooctylbromide nanoparticles via caudal vein. Vital signs of the rats were monitored during the whole study. And echogenic intensity of the liver was dynamically quantified using DFY ultrasound quantified system analysis. The mechanism of contrast enhanced ultrasound(CEUS)and CECT was studied by the frozen sections of rat's organs.Results: The nanoparticles were spherical in appearance, the size and distribution were highly uniformed. Perfluorooctylbromide nanoparticles increased the gray-scale echogenicity of the rat's liver after intravenous injection. 10 s after perfluorooctylbromide nanoparticles administration, The acoustic enhancement of liver began, the peak time was approximately 3～4 min, the duration of contrast enhancement lasted for nearly 1 h. No abnormal changes of the rat's vital signs were observed during the study. Frozen sections suggested that perfluorooctylbromide nanoparticles accumulated gradually in the liver and spleen taking up by macrophages(M?)was one of the potential mechanism of enhancement.Conclusions: Perfluorooctylbromide nanoparticles produced effectively prolonged enhancement of liver in rats, which could be regarded as a potential multimodality(ultrasound/ CT)contrast agent.