Omniparticle Contrast Agent for Multimodal Imaging: Synthesis and Characterization in an Animal Model.

ABSTRACT

PURPOSE: Individual imaging modalities have certain advantages, but each suffers from drawbacks that other modalities may overcome. The goal of this study was to create a novel contrast agent suitable for various imaging modalities that after a single administration can bridge and strengthen the collaboration between the research fields as well as enrich the information obtained from any one modality. PROCEDURES The contrast agent platform is based on dextran-coated iron oxide nanoparticles (for MRI and MPI) and synthesized using a modified co-precipitation method, followed by a series of conjugation steps with a fluorophore (for fluorescence and photoacoustic imaging), thyroxine (for CT imaging), and chelators for radioisotope labeling (for PET imaging). The fully conjugated agent was then tested in vitro in cell uptake, viability, and phantom studies and in vivo in a model of intraductal injection and in a tumor model. RESULTS: The agent was synthesized, characterized, and tested in vitro where it showed the ability to produce a signal on MRI/MPI/FL/PA/CT and PET images. Studies in cells showed the expected concentration-dependent uptake of the agent without noticeable toxicity. In vivo studies demonstrated localization of the agent to the ductal tree in mice after intraductal injection with different degrees of resolution, with CT being the best for this particular application. In a model of injected labeled tumor cells, the agent produced a signal with all modalities and showed persistence in tumor cells confirmed by histology. CONCLUSIONS: A fully functional omniparticle contrast agent was synthesized and tested in vitro and in vivo in two animal models. Results shown here point to the generation of a potent signal in all modalities tested without detrimental toxicity. Future use of this agent includes its exploration in various models of human disease including image-guided diagnostic and therapeutic applications.