Selective disruption of the blood-brain barrier by photochemical internalization
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.
This paper was published in SPIE Proceedings Vol. 7161