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

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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.

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Acknowledgements

The authors would like to thank Gloria Perez for her assistance with autoradiography.

Funding

This work was supported in part by R01 CA221771 and R01 CA261691 to A.M. and R21 CA226579 and R01 CA258314 to L.S.

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Authors and Affiliations

  1. Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA

    Neil Robertson, Lorenzo Sempere, Elizabeth Kenyon, Alan Halim & Anna Moore

  2. Department of Radiology, College of Human Medicine, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA

    Neil Robertson, Lorenzo Sempere, Christiane Mallet, Jeremy Hix, Jinda Fan & Anna Moore

  3. Department of Chemistry, College of Natural Sciences, Michigan State University, 578 S Shaw Lane, East Lansing, MI, 48824, USA

    Neil Robertson, Lorenzo Sempere, Elizabeth Kenyon, Christiane Mallet, Kylie Smith, Jeremy Hix, Alan Halim, Jinda Fan & Anna Moore

  4. Institute for Quantitative Health Science and Engineering, Michigan State University, 775 Woodlot Drive, East Lansing, MI, 48824, USA

    Christiane Mallet, Kylie Smith, Jeremy Hix & Jinda Fan

  5. Department of Biomedical Engineering, College of Engineering, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA

    Kylie Smith & Jinda Fan

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  1. Neil Robertson
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  9. Anna Moore
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Contributions

N.R. designed and synthesized of the compound, wrote the draft of the manuscript; L.S. contributed to the concept, designed the animal model, contributed to data acquisition and analysis, revising the manuscript, and financial support of the study; E.K. contributed to the design of the animal model, data acquisition, and analysis; C.M., K.S., and J.X. contribution to in vitro and in vivo imaging, data acquisition, and analysis; A.H. assisted with cellular work; J.F. contributed to synthesis, radiolabeling, data acquisition, and analysis; A.M. contributed to the concept, revision of the manuscript, data analysis, and financial support of the study.

Corresponding author

Correspondence to Anna Moore.

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Robertson, N., Sempere, L., Kenyon, E. et al. Omniparticle Contrast Agent for Multimodal Imaging: Synthesis and Characterization in an Animal Model. Mol Imaging Biol 25, 401–412 (2023). https://doi.org/10.1007/s11307-022-01770-w

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  • DOI: https://doi.org/10.1007/s11307-022-01770-w

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