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Bioluminescence and MR Imaging of the Safety and Efficacy of Vascular Disruption in Gliomas

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Abstract

Purpose

The goal of the present study was to examine the safety and efficacy of the vascular disrupting agent (VDA) EPC2407 (Crolibulin™) in experimental glioma models using bioluminescence imaging (BLI) and magnetic resonance imaging (MRI).

Procedures

Experimental imaging studies were performed in subcutaneous human U87 glioma xenografts and orthotopic murine gliomas established by intracranial implantation of luciferase-transfected glioma cells (GL261-luc). Correlative histopathology and long-term survival analysis was also performed.

Results

Treatment with EPC2407 decreased tumor perfusion and increased necrosis and tumor doubling times in subcutaneous U87 xenografts. Dynamic BLI and T1-weighted contrast-enhanced MRI showed reduction in blood flow of intracranial GL261-luc gliomas within a few hours of VDA treatment. T2-weighted MRI did not show any evidence of hemorrhaging or edema in uninvolved brain tissue of EPC2407-treated animals. A significant increase in median survival (p < 0.05) was observed in the orthotopic GL261-luc model following VDA treatment compared to untreated controls.

Conclusions

We demonstrate, for the first time, the biological activity of EPC2407 in experimental gliomas. Further investigation into the potential of VDAs in combination with chemoradiation therapy against gliomas is warranted.

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Acknowledgments

The authors would like to thank the technical assistance provided by Marianne Marcotte, Steven Turowski, and the staff of the Laboratory Animal Resource and the Small Animal Bio-Imaging Resource in performing these studies. The authors would also like to thank Dr. Michael Ciesielski for thoughtful discussions and technical assistance in performing these studies. This work was supported by a grant from the American Brain Tumor Association (in honor of Michael Baldasaro) and utilized shared resources supported by the National Cancer Institute P30CA06156 and RPCI Developmental funds.

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Authors and Affiliations

  1. Laboratory for Translational Imaging, Department of Molecular/Cellular Biophysics and Biochemistry, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Margaret Folaron & Mukund Seshadri

  2. Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Margaret Folaron & Mukund Seshadri

  3. Department of Head and Neck Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Mukund Seshadri

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  1. Margaret Folaron
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  2. Mukund Seshadri
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Correspondence to Mukund Seshadri.

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The authors declare that they have no conflict of interest.

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Folaron, M., Seshadri, M. Bioluminescence and MR Imaging of the Safety and Efficacy of Vascular Disruption in Gliomas. Mol Imaging Biol 18, 860–869 (2016). https://doi.org/10.1007/s11307-016-0963-8

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  • DOI: https://doi.org/10.1007/s11307-016-0963-8

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