Temperature dependence of ultrasonic enhancement with a site-targeted contrast agent

Molecular imaging contrast agents specifically detect the biochemical "sign atures" of disease before anatomical manifestations are apparent. Sensitive and specific localization of fibrin both in vivo and in vitro has been dem onstrated with the use of a ligand-directed liquid perfluorocarbon nanopart icle. Since the acoustic properties of perfluorocarbons are known to vary w ith temperature, it was hypothesized that temperature could be used to augm ent the magnitude of enhancement imparted by targeted nanoparticles. Accord ingly, the acoustic backscatter of two different substrates, nitrocellulose membrane and human plasma clot, targeted by the nanoparticles was measured at temperatures ranging from 27 degrees to 47 degreesC in 5 degreesC incre ments. Classic avidin-biotin interactions were utilized to couple biotinyla ted nanoparticles to avidin-conjugated nitrocellulose membranes. Ultrasonic contrast enhancement of the nitrocellulose membrane at 25 MHz, measured by acoustic microscopy, increased from 2.0 +/-0.3 dB at 27 degreesC to 3.7 +/ -0.4 at 47 degreesC. In a similar experiment, antifibrin nanoparticles boun d to human plasma clots also exhibited temperature-dependent ultrasonic sig nal enhancement ranging from 13.9 +/-1.5 dB at 27 degreesC to 18.1 +/-1.5 d B at 47 degreesC. The increase in ultrasonic contrast enhancement measured was well described by a simple, acoustic transmission line model with tempe rature-dependent impedance. These results suggest that temperature-dependen t changes in acoustic backscatter may be used to further differentiate tiss ues targeted with site-specific nanoparticles from surrounding normal soft tissues. (C) 2001 Acoustical Society of America.