Targeting of ultrasound contrast material - An in vitro feasibility study

Purpose: It would be beneficial to design a targetable microbubble ultrasound contrast agent that would selectively bind to the areas of interest in the body and enhance the target organ in the ultrasound examination. Material and Methods: We have studied the feasibility of targeting in a model system. We used avidin and biotin as a model ligand-receptor pair. Avidin was adsorbed on the surface of polystyrene, and biotin derivative was attached to microbubble shells. After removal of unincorporated biotin from the microbubbles, they were allowed to come in contact with avidin-coated or albumin-coated plastic. Unbound bubbles were washed by a stream of water. Results: Binding of microbubbles to the surface occurred selectively in the areas where avidin layer was deposited. Binding of microbubbles to avidin layer was dependent on the amount of biotin incorporated in the microbubble shell. Presence of free biotin blocked targeting completely. Acoustic studies were performed using a custom-built ultrasound measurement apparatus and an ultrasound medical imaging system. Microbubble-coated areas of the plastic dish were clearly visualized with ultrasound imaging. A strong backscattered signal was obtained for microbubble surface densities as low as 3%. Conclusion: Microbubbles have been selectively targeted via a ligand-receptor system in vitro. Firm binding of microbubbles to avidin-coated surface has been achieved. Microbubbles deposited on the target were visualized with ultrasound imaging systems.