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Synthesis of Ultrasound Contrast Agent: Characteristics
and Size Distribution Analysis |
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Hak Jong Lee, MD1, 2 Tae Jong Yoon, MD3, Young Il Yoon, MD1 |
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1Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul
National University Graduate School of Convergence Science and Technology
2Department of Radiology, Seoul National University College of Medicine and Seoul National
University Bundang Hospital
3Department of Applied Bioscience, CHA University |
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Purpose: The purpose of this study is to establish the methodology regarding synthesis
of ultrasound contrast agent imaging, and to evaluate the characteristics of the
synthesized ultrasound contrast agents, including size or degradation interval and
image quality.
Materials and Methods: The ultrasound contrast agent, composed of liposome
and SF6, was synthesized from the mixture solution of 21 μmol DPPC (1, 2-
Dihexadecanoyl-sn-glycero-3-phosphocholine, C40H80NO8P), 9 μmol cholesterol, 1.9
μmol of DCP (Dihexadecylphosphate, [CH3(CH2)15O]2P(O)OH), and chloroform. After
evaporation in a warm water bath and drying during a period of 12-24 hours, the contrast
agent was synthesized by the sonication process by addition of buffer and SF6
gas. The size of the contrast agent was controlled by use of either extruder or sonication
methods. After synthesis of contrast agents, analysis of the size distribution of the
bubbles was performed using dynamic light scattering measurement methods. The
degradation curve was also evaluated by changes in the number of contrast agents
via light microscopy immediate, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72
hours, and 84 hours after synthesis. For evaluation of the role as an US contrast
agent, the echogenicity of the synthesized microbubble was compared with commercially
available microbubbles (SonoVue, Bracco, Milan, Italy) using a clinical ultrasound
machine and phantom.
Results: The contrast agents were synthesized successfully using an evaporationdrying-
sonication method. The majority of bubbles showed a mean size of 154.2
nanometers, and they showed marked degradation 24 hours after synthesis. ANOVA
test revealed a significant difference among SonoVue, synthesized contrast agent,
and saline (p < 0.001). Although no significant difference was observed between
SonoVue and the synthesized contrast agent, difference in echogenicity was
observed between synthesized contrast agent and saline (p < 0.01).
Conclusion: We could synthesize ultrasound contrast agents using an evaporation-
drying-sonication method. On the basis of these results, many prospective types
of research, such as anticancer drug delivery, gene delivery, including siRNA or
microRNA, targeted molecular imaging, and targeted therapy can be performed. |
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Keyword : Ultrasound; Contrast agent; Synthesis; Drug delivery; Image guided therapy |
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pdf파일 : 59-65이학종08.pdf
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