Selective disruption of the blood-brain barrier by photochemical internalization

Henry Hirschberg, Michelle J. Zhang, Michael H. Gach, Francisco A. Uzal, David Chighvinadze, Steen J. Madsen

Research output: Contribution to journalConference articlepeer-review

1 Scopus citations

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 AlPcS 2a-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.

Original languageEnglish
Article number716136
JournalProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume7161
DOIs
StatePublished - Jun 8 2009
EventPhotonic Therapeutics and Diagnostics V - San Jose, CA, United States
Duration: Jan 24 2009Jan 26 2009

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