Measurements of lifetime and attenuation properties of ultrasound/magnetic resonance multimodality molecular probe

It has been shown that microbubble (MB)-enhanced focused ultrasound (FUS) temporally and locally disrupts the blood-brain barrier (BBB), thereby enhancing drug delivery into brain tumors. Imaging tumor angiogenesis with contrast-enhanced ultrasound (US) has been explored with targeted MBs. The BBB opening threshold and BBB opening volume were found to be bubble-size-dependent. However, the relationships between the various components of bubble shells and BBB opening are still unclear. According to a previous study, 1-2 μm bubbles have the most pronounced acoustic activity at frequencies above 10 MHz. The present study developed targeted US/magnetic resonance (MR) multimodality MBs, whose acoustic properties were compared with two commercial MBs, namely SonoVue and Targestar SA. The acoustic activities of these 1.15-2.78 /im MBs with different shells at 10 MHz were investigated. The lifetime and attenuation properties of lipid MBs (SonoVue and Targestar SA), albumin-(Gd-DTPA) MBs, and avidin-conjugated albumin (avidin-albumin)-(Gd-DTPA) MBs at 10 MHz were investigated with the pulse-echo substitution method. It was found that incorporating avidin into the albumin MBs and albumin-(Gd-DTPA) MBs affects the size distribution but does not affect the concentration of MBs produced. The avidin-albumin-shelled MBs had more significant nonlinear activity at 4-18 MHz (p = 0.025), whereas the nonlinear activity of the other MBs peaked at 6-24 MHz (p = 0.003-0.044). Moreover, the incorporation of paramagnetic metal ions into the MB shells increased their attenuation coefficients. With regard to the lifetime of these agents, the attenuations of the SonoVue and Targestar SA were 87.96% and 8.74%, respectively, and those of albumin, avidin-albumin, albumin-(Gd-DTPA), and avidin-albumin-(Gd-DTPA) MBs were 49.52%, 41.38%, 74.69%, and 100%, respectively. Avidin conjugation decreased the lifetime of the albumin MBs, but not that of the lipid MBs. The incorporation of paramagnetic metal ions into the shells of albumin MBs did not decrease their lifetime.