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Proceedings Paper

Selective disruption of the blood-brain barrier by photochemical internalization
Author(s): Henry Hirschberg; Michelle J. Zhang; Michael H. Gach; Francisco A. Uzal; David Chighvinadze; Steen J. Madsen
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Paper Abstract

Introduction: Failure to eradicate infiltrating glioma cells using conventional treatment regimens results in tumor recurrence and is responsible for the dismal prognosis of patients with glioblastoma multiforme (GBM). This is due to the fact that these migratory cells are protected by the blood-brain barrier (BBB) which prevents the delivery of most anti-cancer agents. We have evaluated the ability of photochemical internalization (PCI) to selectively disrupt the BBB in rats. This will permit access of anti-cancer drugs to effectively target the infiltrating tumor cells, and potentially improve the treatment effectiveness for malignant gliomas. Materials and Methods: PCI treatment, coupling a macromolecule therapy of Clostridium perfringens (Cl p) epsilon prototoxin with AlPcS2a-PDT, was performed on non-tumor bearing inbred Fisher rats. T1-weighted post-contrast magnetic resonance imaging (MRI) scans were used to evaluate the extent of BBB disruption which can be inferred from the volume contrast enhancement. Results: The synergistic effect of PCI to disrupt the BBB was observed at a fluence level of 1 J with an intraperitoneal injection of Cl p prototoxin. At the fluence level of 2.5J, the extent of BBB opening induced by PCI was similar to the result of PDT suggesting no synergistic effect evoked under these conditions. Conclusion: PCI was found to be highly effective and efficient for inducing selective and localized disruption of the BBB. The extent of BBB opening peaked on day 3 and the BBB was completed restored by day 18 post treatment.

Paper Details

Date Published: 23 February 2009
PDF: 8 pages
Proc. SPIE 7161, Photonic Therapeutics and Diagnostics V, 716136 (23 February 2009); doi: 10.1117/12.810552
Show Author Affiliations
Henry Hirschberg, Beckman Laser Institute, Univ. of California, Irvine (United States)
Univ. of Nevada, Las Vegas (United States)
Michelle J. Zhang, Univ. of Nevada, Las Vegas (United States)
Michael H. Gach, Nevada Cancer Institute (United States)
Francisco A. Uzal, Univ. of California, Davis (United States)
David Chighvinadze, Univ. of Nevada, Las Vegas (United States)
Steen J. Madsen, Univ. of Nevada, Las Vegas (United States)
Nevada Cancer Institute (United States)

Published in SPIE Proceedings Vol. 7161:
Photonic Therapeutics and Diagnostics V
Henry Hirschberg M.D.; Brian Jet-Fei Wong M.D.; Kenton W. Gregory M.D.; Reza S. Malek; Nikiforos Kollias; Bernard Choi; Guillermo J. Tearney; Justus F. R. Ilgner; Steen J. Madsen; Laura Marcu; Haishan Zeng, Editor(s)

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