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30.08.2016 | Laboratory Investigation

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

verfasst von: Jason A. Ellis, Johann Cooke, Rajinder P. Singh-Moon, Mei Wang, Jeffrey N. Bruce, Charles W. Emala, Irving J. Bigio, Shailendra Joshi

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2016

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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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Titel: Safety, feasibility, and optimization of intra-arterial mitoxantrone delivery to gliomas
verfasst von: Jason A. Ellis
Johann Cooke
Rajinder P. Singh-Moon
Mei Wang
Jeffrey N. Bruce
Charles W. Emala
Irving J. Bigio
Shailendra Joshi
Publikationsdatum: 30.08.2016
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology / Ausgabe 3/2016
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-016-2253-3

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