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In Vivo Performance of a Liposomal Vascular Contrast Agent for CT and MR-Based Image Guidance Applications

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Abstract

Purpose

This study evaluated the in vivo performance of a liposome formulation that co-encapsulates iohexol and gadoteridol as a multimodal contrast agent for computed tomography (CT) and magnetic resonance (MR)-based image guidance applications.

Materials and Methods

The pharmacokinetics and biodistribution studies were conducted in Balb-C mice using high performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission spectrometry (ICP-AES) to detect iohexol and gadoteridol concentrations. The imaging efficacy of this liposome system was assessed in New Zealand White rabbits using a clinical CT and a clinical 1.5 Tesla MR scanner.

Results

The vascular half-lives of the liposome encapsulated iohexol and gadoteridol in mice were found to be 18.4 ± 2.4 and 18.1 ± 5.1 h. When administered at the same dose the distribution (α phase) half-lives for the free contrast agents were 12.3 ± 0.5 min (iohexol) and 7.6 ± 0.9 min (gadoteridol); while, the elimination (β phase) half-lives were 3.0 ± 0.9 h for free iohexol and 3.0 ± 1.3 h for free gadoteridol. The CT and MR signal increases were measured and correlated with the concentrations of iohexol and gadoteridol detected in plasma samples.

Conclusion

The long in vivo circulation lifetime and simultaneous CT and MR signal enhancement provided by this liposome system make it a promising agent for image guidance applications.

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Acknowledgements

This work is funded in-part by a CIHR Operating Grant and a CIHR Proof of Principle Grant to D.A. Jaffray and C. Allen, the Premier’s Research Excellence Award, the Fidani Chair in Radiation Physics and the Grange Advanced Simulation Initiative. J. Zheng is grateful for the Excellence in Radiation Research for the 21st Century Training Fellowship and the Mitchell Scholarship. The authors would like to thank the UHN animal care staff for their assistance.

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Authors and Affiliations

  1. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    Jinzi Zheng & David A. Jaffray

  2. Department of Pharmaceutical Sciences, University of Toronto, 144 College Street, Room 1203, Toronto, Ontario, M5S 3M2, Canada

    Jubo Liu, Mike Dunne & Christine Allen

  3. Radiation Medicine Program, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada

    David A. Jaffray

  4. Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada

    David A. Jaffray

  5. Department of Chemistry, University of Toronto, Toronto, Ontario, Canada

    Christine Allen

  6. Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada

    Christine Allen

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  1. Jinzi Zheng
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  4. David A. Jaffray
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Correspondence to Christine Allen.

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Zheng, J., Liu, J., Dunne, M. et al. In Vivo Performance of a Liposomal Vascular Contrast Agent for CT and MR-Based Image Guidance Applications. Pharm Res 24, 1193–1201 (2007). https://doi.org/10.1007/s11095-006-9220-1

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  • DOI: https://doi.org/10.1007/s11095-006-9220-1

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