Gas Microbubbles: from ultrasound contrast agent to therapeutic agent

Jean-Marc HYVELIN, Bracco Suisse SA

Since the introduction of the first commercial ultrasound contrast agents (UCA), so called microbubbles (MB), in the nineties, substantial improvement has been accomplished. Today, four UCA are commercially available, namely Definity®, Sonazoid®, SonoVue® (also marketed as Lumason™ in the USA) and Optison®. After a relatively long period of acceptance, contrast enhanced ultrasound (CEUS) has now reached the stage of maturity and has demonstrated a continuous increase in market share over the years, primarily due to its sensitive, safe, inexpensive and portable nature. In mid-2000, Bracco further demonstrated its commitment of improving diagnostic ultrasound by entering into the area of ultrasound molecular imaging (USMI), aiming at early diagnosis and individually tailored treatments. The first example of its clinically translatable USMI agent is BR55, whose targeting relies on a ligand specific for the vascular endothelial growth factor receptor 2 (VEGFR2). Positive pre-clinical proof of concept has prompted Bracco to move a step further, and evaluate the potency of BR55 in clinic for the detection and characterization of breast, ovary and prostate cancer. More recently, the development of another clinically translatable USMI agent called Microbubble-Selectin (MBSelectin) has been initiated at Bracco. Its targeting relies on a ligand specific for vascular markers which are overexpressed during inflammation. Beside the use of UCA for diagnostic applications, MBs also possess unique properties for therapeutic applications. In that respect, exploitation of the mechanical property of cavitation generated by gas microbubbles under ultrasound field has proven to be useful to allow vessel recanalization – so-called sonothrombolysis – that could be applied to stroke and also  myocardial application. Another emerging application is to alter vessel permeability to improve drug/genes delivery into specific organ (e.g. brain) or lesions (e.g. cancer…).

The purpose of this lecture will be to give an update of Bracco GR&D’s activity in the field of UCA. More precisely,  it will illustrate that ultrasound contrast agents can be versatile agents providing both diagnostic and potentially therapeutic value.

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