Ultrasound Contrast Agents for Molecular Imaging

Abstract

The successful use of targeted ultrasound contrast agents (USCAs) for qualitative US-based imaging has been shown by several academic and industrial research groups in different animal models. Furthermore, techniques have been developed that enable the in-vivo quantification of targeted microbubbles (MBs). USCAs for quantitative functional and molecular imaging in small animals can be used for a more detailed characterization of new and established disease models and provide quantitative biological insights into the interaction between drug and target or target and disease in living animals. The advantages of such contrast agents in research and development are seen to be as follows: new functional or molecular findings in the complex biology of disease development, these findings can lead to new therapeutic strategies or drug candidates, a better understanding of the treatment effects of new and existing drug candidates, a more sensitive and specific characterization of early treatment effects in living animals, identification of in-vivo biomarkers for translational medicine. Further outcomes are seen in speeding up the evaluation of new drug compounds and in a reduction of the number of animals used for biomedical research.

Biogenic gas nanostructures as ultrasonic molecular reporters

“…Their ability to produce stable contrast at sub-nanomolar reporter concentrations may enable future applications of ultrasound in imaging studies that, to date, have been dominated by nanoparticle reporters for other modalities such as MRI and fluorescence 14 . These concentrations represent gas contents (< 1 µL gas / mL solution) similar to or smaller than those of typical formulations of microbubbles, which contain approximately 10 3 times more gas per particle 19 . Furthermore, several of the demonstrated acoustic properties, including response at high frequencies (up to the measured 18 MHz), ability to produce harmonic signals (in Halo GVs) and controlled acoustic collapsibility in situ, are especially advantageous for high-resolution contrast-enhanced imaging 24 .…”

“…2d, e ). Such subtraction images can be used to increase the specificity of contrast information relative to background scattering 19 .…”

Molecular Imaging with Bioconjugates in Mouse Models of Cancer

“…These developments hinge upon a combination of (i) the use of very high frequency probes, which emit sound waves with frequencies up to 100 MHz and result in a very high imaging resolution of the order of 25 µm, and (ii) ultrasound contrast agents based on the use of gas-filled microbubbles, although since such agents are too large to leave the vascular space, their application is limited to intravascular structures such as endothelial target molecules. A tradeoff against the excellent resolution of highfrequency ultrasound is its poor tissue penetration, and the sensitivity of detection of contrast agents is low (48). Modern semiautomated small animal ultrasound systems overcome to some extent the intraoperator variability of this modality, but it should still be considered a generally qualitative rather than quantitative tool.…”

Concentration estimation of ultrasound targeted microbubbles for improving cancer detection: A preliminary in VIVO study

“…UCAs are solutions composed of micron-sized gas bubbles protected by a shell of different nature (e.g., lipidic or polymeric shells). Starting from the concept that microbubbles passively flow in vessels like red blood cells, targeted contrast agents have been developed in order to extend ultrasound imaging to the depiction of molecular and cellular processes [2]. Targeted ultrasound imaging involves the design and synthesis of microbubbles able to adhere to endothelium or other targets under disease-specific conditions.…”