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Interstitial continuous infusion therapy in a malignant glioma model in rats

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Abstract

Purpose

Local direct delivery of chemotherapeutic agents for the treatment of brain tumors is an area of focus in the development of new therapeutic paradigms. These techniques need improvement, especially in terms of drug retention in brain tissue.

Materials and methods

In this study, we used a rat glioma model to examine carboplatin distribution, as measured by platinum penetration, after delivery via interstitial continuous (i.c.) infusion. We also examined rat survival times in response to carboplatin and oxaliplatin. I.C. infusion, a modified version of convection-enhanced delivery (CED) for local drug delivery, uses low volume (1 μl per hour) continuous infusion directly into the tumor.

Results

I.C. infusion produced a nearly 360-fold higher concentration of platinum in tumor tissue and significantly prolonged rodent survival time compared to intraperitoneal (i.p.) infusion.

Conclusions

We showed i.c. infusion allows for circumvention of the blood–brain barrier, focused drug distribution, and sustained drug delivery. This method could be a promising strategy for treating brain tumors.

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Acknowledgments

This project was supported by the Rory David Deutsch Foundation, the Neuro-Oncology Research Foundation of Children’s Memorial Hospital, Chicago, Illinois and the Dr. Ralph and Marian C. Falk Medical Research Trust, Chicago, Illinois. We acknowledge expert technical assistance provided by Christopher D. McCabe, M.S. and Julianne Holleran (Medicine and Pharmacology, University of Pittsburgh Cancer Institute, Pittsburgh), The Department of Pathology Laboratory and Medicine, Children’s Memorial Hospital, Chicago, Illinois, and the editorial assistance of Rishi Lulla, M.D. and Ms. Terrie Byrne.

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Authors and Affiliations

  1. Division of Pediatric Neurosurgery, Children’s Memorial Hospital, 2300 Children’s Plaza Box#28, Chicago, IL, 60614, USA

    Yuichi Tange, Akihide Kondo, Georgy M. Daneriallis, Hiromichi Nakazaki & Tadanori Tomita

  2. Cancer Biology and Epigenomics Program, Department of Pediatrics, Children’s Memorial Medical Center, Northwestern University, Feinberg School of Medicine, 2300 Children’s Plaza, Chicago, IL, 60614, USA

    Akihide Kondo, Simone T. Sredni & Marcelo B. Soares

  3. University of Pittsburgh Cancer Institute, Room G27E, Hillman Research Pavilion 5117 Centre Avenue, Pittsburgh, PA, 15213, USA

    Merrill J. Egorin

  4. Department of Biological Sciences, Purdue University Calumet, 2200 169th street, Hammond, IN, 46323, USA

    Barbara Mania-Farnell

  5. Division of Hematology/Oncology/Transplantation, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL, 60614, USA

    Stewart Goldman

  6. Division of Anatomic Pathology, Children’s Memorial Hospital, 2300 Children’s Plaza, Chicago, IL, 60614, USA

    Veena Rajaram

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  1. Yuichi Tange
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  2. Akihide Kondo
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  8. Veena Rajaram
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  9. Stewart Goldman
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  11. Tadanori Tomita
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Corresponding author

Correspondence to Akihide Kondo.

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Tange, Y., Kondo, A., Egorin, M.J. et al. Interstitial continuous infusion therapy in a malignant glioma model in rats. Childs Nerv Syst 25, 655–662 (2009). https://doi.org/10.1007/s00381-008-0805-3

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  • DOI: https://doi.org/10.1007/s00381-008-0805-3

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