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MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct

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Abstract

A genetically modified ferritin has been examined for its properties as a tumor-selective magnetic resonance imaging (MRI) contrast agent. The engineered ferritin described herein was derived from Archaeoglobus fulgidus (AfFtn-AA), which stores a significantly greater quantity of iron than wild-type ferritins. Relaxivity measurements were taken at 3 Tesla of ferritin particles uniformly distributed in an agarose gel to assess relaxivities r 1 and r 2. The r 1 and r 2 values of the uniformly distributed modified ferritin were significantly higher (r 1 = 1,290 mM−1 s−1 and r 2 = 5,740 mM−1 s−1) than values observed for wild-type ferritin (e.g., horse spleen, r 1 = 0.674 mM−1 s−1, r 2 = 95.54 mM−1 s−1). The modified iron-enriched ferritin (14.5 nm diameter) was conjugated with a monoclonal antibody (10 nm length) against rat Necl-5, a cell surface glycoprotein overexpressed by many epithelial cancers. In vitro studies showed strong reactivity of the assembled nanoconjugate to transformed Necl-5 positive rat prostate epithelial cells. Furthermore, MRI demonstrated a significant T2 contrast with negligible T1 effect when bound to cells. These findings highlight the utility of the modified ferritin construct as a novel MRI contrast agent that can be manipulated to target antigen-specific tissues.

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Abbreviations

MRI:

Magnetic resonance imaging

DTPA:

Diethylenetriaminepentaacetic acid

BDEC:

Rat bile duct epithelial cells

PEC:

Prostate epithelial cells

Necl-5:

Nectin-like molecule 5

TR:

Repetition time

TE:

Echo time

SPION:

Superparamagnetic iron oxide nanoparticle

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Acknowledgments

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number P20GM103421. The previous segment of this project was supported by the National Center for Research Resources (NCRR) under P20 RR 017695. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research support was also provided by a grant from the Brown University/Lifespan Department of Diagnostic Imaging under award number 2010-3, Lifespan Research Seed Grant 2012, and Academic Research Fund Tier 1 from Singapore Ministry of Education (RG33/07).

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Authors and Affiliations

  1. Department of Neuroscience, Brown University, Box GL-N, Providence, RI, 02912, USA

    Edward G. Walsh

  2. Department of Diagnostic Imaging, Rhode Island Hospital, Providence, RI, USA

    Edward G. Walsh & William K. C. Park

  3. Institute for Brain Science, Brown University, Providence, RI, USA

    Edward G. Walsh

  4. Division of Hematology and Oncology, Department of Medicine, Rhode Island Hospital/Warren Alpert Medical School of Brown University, Providence, RI, USA

    David R. Mills & Kate E. Brilliant

  5. Division of Bioengineering, Nanyang Technological University, Singapore, Singapore

    Sierin Lim & Barindra Sana

  6. Division of Molecular Imaging, Rhode Island Hospital/Warren Alpert Medical School of Brown University, Providence, RI, USA

    William K. C. Park

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  1. Edward G. Walsh
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Correspondence to Edward G. Walsh.

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Walsh, E.G., Mills, D.R., Lim, S. et al. MRI contrast demonstration of antigen-specific targeting with an iron-based ferritin construct. J Nanopart Res 15, 1409 (2013). https://doi.org/10.1007/s11051-012-1409-0

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  • DOI: https://doi.org/10.1007/s11051-012-1409-0

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