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A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging

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Abstract

Purpose

This study aims to develop a low molecular weight folate receptor (FR) contrast agent for MR tumor imaging.

Procedures

Gadolinium-tetraazacyclododecane tetraacetic acid (Gd.DOTA) was conjugated to folic acid to create Gd.DOTA.Folate. The efficacy of Gd.DOTA.Folate to bind FR was evaluated in vitro by inductively coupled mass spectrometry (ICP-MS) and in vivo by magnetic resonance imaging (MRI) tumor enhancement over 14 h, utilizing an overexpressing α-FR cell line (IGROV-1), compared to an α-FR-negative cell line (OVCAR-3). Gd.DOTA.Folate localization ex vivo was verified by laser ablation ICP-MS.

Results

ICP-MS confirmed Gd.DOTA.Folate uptake by IGROV-1 cells and competitive binding with free folic acid inhibited binding. IGROV-1 tumors showed an increase in R 1 at 2 h, which increased significantly over 14 h post-Gd.DOTA.Folate with clear enhancement on MR images. This was not observed in controls.

Conclusion

These data support the use of FR-targeted small molecular weight MRI contrast agents for tumor imaging in vivo.

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Acknowledgment

Funding for Tammy Kalber was provided by the MRC. The GTC is supported by EPSRC grant and is grateful for recent support from ImuThes Limited. The authors would also like to thank Mahamoud O. Hussein for his contribution to the chemical synthesis as well as Catherin Unsworth and Stanislav Strekopytov from the Department of Mineralogy at the Natural History Museum London for their expertise in running ICP-MS of the samples.

Conflict of Interest Disclosure

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK

    Tammy L. Kalber, Nazila Kamaly & Jimmy D. Bell

  2. Imperial College Genetic Therapies Centre, Department of Chemistry, Imperial College London, Flowers Building, Armstrong Road, London, SW7 2AZ, UK

    Nazila Kamaly, Michael R. Jorgensen & Andrew D. Miller

  3. Biological Imaging Centre, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK

    Po-Wah So

  4. Centre for Analytical Sciences, Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK

    John A. Pugh, Josephine Bunch & Cameron W. McLeod

Authors
  1. Tammy L. Kalber
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  2. Nazila Kamaly
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Correspondence to Tammy L. Kalber.

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Kalber, T.L., Kamaly, N., So, PW. et al. A Low Molecular Weight Folate Receptor Targeted Contrast Agent for Magnetic Resonance Tumor Imaging. Mol Imaging Biol 13, 653–662 (2011). https://doi.org/10.1007/s11307-010-0400-3

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  • DOI: https://doi.org/10.1007/s11307-010-0400-3

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