Targeted opening of the blood brain barrier by ALA-mediated photodynamic therapy

Background and Objective: We have evaluated the ability of ALA-mediated PDT to selectivly open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Study Design/Materials and Methods: ALA-PDT was performed on non-tumor bearing inbred Fischer rats at increasing fluence levels. Contrast T1-weighted high field (3 T) magnetic resonance imaging (MRI) scans were used to monitor the degree of BBB disruption. Results: PDT at increasing fluence levels between 9 and 17 J demonstrated an increasing contrast flow rate. The BBB was found to be disrupted 2 h following PDT and 80 - 100 % restored 72 h later at the lowest fluence level. No effect on the BBB was observed if 26 J of light was given in the absence of ALA. Conclusion: ALA-PDT was highly effective in opening the BBB in a localized region of the brain. The degradation of the BBB was temporary in nature at fluence levels of 9 J, opening rapidly following treatment and significantly restored during the next 72 h. No signs of permanent tissue damage were seen on histological sections at this fluence level.

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