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Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

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Abstract

Purpose

In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications.

Procedures

A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions.

Results

These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres.

Conclusions

Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance.

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Acknowledgements

This research was supported in part by grants from the National Institutes of Health (Roadmap Initiative, NIBIB R21 EB005321, NIBIB R01 EB009073, and NCI RC1 CA147096).

Conflicts of Interest

Stephen A. Boppart receives royalties related to optical coherence tomography for patents licensed by the Massachusetts Institute of Technology. He is also co-founder of Diagnostic Photonics, Inc., a company developing Interferometric Synthetic Aperture Microscopy for medical applications, and he receives funding for sponsored research projects from Welch Allyn, Inc. and Samsung, Inc., related to optical imaging technologies. All other authors report no real or perceived conflicts of interest.

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Authors and Affiliations

  1. Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana, 61801, IL, USA

    Renu John, Freddy T. Nguyen, Eric J. Chaney, Marina Marjanovic, Kenneth S. Suslick & Stephen A. Boppart

  2. Department of Chemistry, University of Illinois at Urbana-Champaign, 505 South Mathews Avenue, Urbana, 61801, IL, USA

    Freddy T. Nguyen, Kenneth J. Kolbeck & Kenneth S. Suslick

  3. Medical Scholars Program, University of Illinois at Urbana-Champaign, 506 South Mathews Avenue, Urbana, 61801, IL, USA

    Freddy T. Nguyen & Stephen A. Boppart

  4. Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, 1406 West Green Street, Urbana, 61801, IL, USA

    Stephen A. Boppart

  5. Department of Bioengineering, University of Illinois at Urbana-Champaign, 1304 West Springfield Avenue, Urbana, 61801, IL, USA

    Stephen A. Boppart

  6. Department of Internal Medicine, College of Medicine, University of Illinois at Urbana-Champaign, 506 South Mathews Avenue, Urbana, 61801, IL, USA

    Stephen A. Boppart

Authors
  1. Renu John
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  2. Freddy T. Nguyen
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  3. Kenneth J. Kolbeck
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  4. Eric J. Chaney
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  5. Marina Marjanovic
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  6. Kenneth S. Suslick
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  7. Stephen A. Boppart
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Corresponding author

Correspondence to Stephen A. Boppart.

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John, R., Nguyen, F.T., Kolbeck, K.J. et al. Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents. Mol Imaging Biol 14, 17–24 (2012). https://doi.org/10.1007/s11307-011-0473-7

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  • DOI: https://doi.org/10.1007/s11307-011-0473-7

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