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Safety, feasibility, and optimization of intra-arterial mitoxantrone delivery to gliomas

  • Laboratory Investigation
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Abstract

Mitoxantrone is a highly cytotoxic antineoplastic drug, however, its poor penetration of the blood–brain barrier has limited its role in the treatment of brain cancers. We hypothesize that intra-arterial (IA) delivery of mitoxantrone may enhance its capacity for regional brain deposition thus expanding its potential as a brain tumor therapy agent. In this study we assessed the dose-response characteristics as well as the feasibility and safety of mitoxantrone delivery to the brain and specifically to gliomas in a rodent model. We show that delivery optimization utilizing the technique of intra-arterial transient cerebral hypoperfusion (IA-TCH) facilitates achieving the highest peak- and end- brain drug concentrations as compared to intravenous and IA delivery without hypoperfusion. Additionally, we observed significant tumor-specific uptake of mitoxantrone when delivered by the IA-TCH method. No untoward effects of IA-TCH delivery of mitoxantrone were observed. The IA-TCH method is shown to be a safely tolerated and feasible strategy for delivering mitoxantrone to tumors in the glioma model tested. Additional investigation is warranted to determine if IA-TCH delivery of mitoxantrone produces clinically relevant benefit.

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Funding

This study was funded by the National Cancer Institute at the National Institutes of Health (RO1-CA-138643).

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Authors and Affiliations

  1. Department of Neurological Surgery, Columbia University Medical Center, New York, NY, USA

    Jason A. Ellis & Jeffrey N. Bruce

  2. Department of Electrical Engineering, Columbia University, New York, NY, USA

    Rajinder P. Singh-Moon

  3. Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA

    Johann Cooke, Mei Wang, Charles W. Emala & Shailendra Joshi

  4. Departments of Electrical and Biomedical Engineering, Boston University, Boston, MA, USA

    Irving J. Bigio

Authors
  1. Jason A. Ellis
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  2. Johann Cooke
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  3. Rajinder P. Singh-Moon
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  4. Mei Wang
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  5. Jeffrey N. Bruce
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  6. Charles W. Emala
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  7. Irving J. Bigio
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  8. Shailendra Joshi
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Corresponding author

Correspondence to Jason A. Ellis.

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The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in this study were in accordance with the ethical standards of the Columbia University Institutional Review Board and the Animal Care and Use Committee.

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Ellis, J.A., Cooke, J., Singh-Moon, R.P. et al. Safety, feasibility, and optimization of intra-arterial mitoxantrone delivery to gliomas. J Neurooncol 130, 449–454 (2016). https://doi.org/10.1007/s11060-016-2253-3

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  • DOI: https://doi.org/10.1007/s11060-016-2253-3

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