Ultrasonography.  2017 Oct;36(4):378-384. 10.14366/usg.17014.

Synthesis of ultrasound contrast agents: characteristics and size distribution analysis (secondary publication)

Affiliations
  • 1Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Seoul, Korea. hakjlee@snu.ac.kr
  • 2Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 3Department of Applied Bioscience, CHA University, Pocheon, Korea.

Abstract

PURPOSE
The purpose of this study was to establish a method for ultrasound (US) contrast agent synthesis and to evaluate the characteristics of the synthesized US contrast agent.
METHODS
A US contrast agent, composed of liposome and sulfur hexafluoride (SF₆), was synthesized by dissolving 21 μmol 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC, C₄₀H₈₀NO₈P), 9 μmol cholesterol, and 1.9 μmol of dihexadecylphosphate (DCP, [CH₃(CH₂)15O]₂P(O)OH) in chloroform. After evaporation in a warm water bath and drying for 12-24 hours, the contrast agent was synthesized using the sonication process by the addition of a buffer and SF₆ gas. The size distribution of the bubbles was analyzed using dynamic light scattering measurement methods. The degradation curve was evaluated by assessing the change in the number of contrast agent bubbles using light microscopy immediately, 12, 24, 36, 48, 60, 72, and 84 hours after synthesis. The echogenicity of the synthesized microbubbles was compared with commercially available microbubbles (SonoVue, Bracco).
RESULTS
contrast agent was synthesized successfully using an evaporation-drying-sonication method. Most bubbles had a mean diameter of 154.2 nm and showed marked degradation 24 hours after synthesis. Although no statistically significant differences were observed between SonoVue and the synthesized contrast agent, a difference in echogenicity was observed between the synthesized contrast agent and saline (P<0.01).
CONCLUSION
We successfully synthesized a US contrast agent using an evaporation-dryingsonication method. These results may help future research in the fields of anticancer drug delivery, gene delivery, targeted molecular imaging, and targeted therapy.

Keyword

Ultrasound; Contrast media; Synthesis; Drug delivery systems; Radiotherapy, image guided

MeSH Terms

Baths
Chloroform
Cholesterol
Contrast Media*
Drug Delivery Systems
Dynamic Light Scattering
Liposomes
Methods
Microbubbles
Microscopy
Molecular Imaging
Radiotherapy, Image-Guided
Sonication
Sulfur Hexafluoride
Ultrasonography*
Water
Chloroform
Cholesterol
Contrast Media
Liposomes
Sulfur Hexafluoride
Water
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