Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 32, Issue 1, Pages 83-93Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2005.08.009
Keywords
ultrasound; contrast agent; nanometer; surfactant-stabilized; harmonic imaging; differential centrifugation; angiogenesis targeting
Funding
- NCI NIH HHS [CA52823] Funding Source: Medline
- NHLBI NIH HHS [HL 52901] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA052823] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL052901] Funding Source: NIH RePORTER
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Ultrasound contrast agents (CA) are generally micron-sized stabilized gas bubbles, injected IV. However, to penetrate beyond the vasculature and accumulate in targets such as tumors, CA must be an order of magnitude smaller. We describe a method of achieving nanometer-sized, surfactant-stabilized CA by differential centrifugation. High g force was shown to destroy bubble integrity. Optimal conditions (300 rpm for 3 min) produced an agent with a mean diameter of 450 nm, which gave 25.5 dB enhancement in vitro at a dose of 10 mu L/mL, with a 13 min half-life. In vivo, the CA produced excellent power Doppler and grey-scale pulse inversion harmonic images at low acoustic power when administered. In vivo dose-response curves obtained in three rabbits showed enhancement between 20 and 25 dB for dosages above 0.025 mL/kg. These results encourage further investigation of the possible diagnostic and therapeutic benefits of using nanoparticles as CA, including passive targeting and accumulation in tumors.
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