Cerebral edema following photodynamic therapy using endogenous and exogenous photosensitizers in normal brain

Background and Objective Failure of treatment for high-grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy such as photodynamic therapy (PDT) could be of benefit. The increase in brain edema following PDT using endogenous and exogenous photosensitizers was compared in terms of animal survival, MR imaging, and histopathological changes in normal brain. Materials and Methods Fischer rats were exposed to increasing laser light treatment following intraperitoneal injection of either the photosensitizers 5-aminolevulinic acid (ALA) or aluminum phthalocyanine disulfonate (AlPcS2a). Light treatment was applied either via an optical fiber inserted directly into the brain parenchyma or through a fiber applied to the surface of the intact skull. Edema development was followed by T2-weighted MR imaging. Results ALA and AlPcS2a PDT resulted in a fluence dependent increase in cerebral edema and mortality. AlPcS2a PDT showed significant edema and mortality even at low fluences following interstitial light delivery, which was reduced with surface illumination. The mechanism of edema was determined to be vasogenic by response to steroid therapy and confirmed on histological images. Conclusions T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and noninvasive modality in following the development of the edema reaction and the degree and time course of blood-brain barrier dysfunction thus allowing the use of fewer animals. ALA mediated PDT induced a lower edema reaction than that observed with the photosensitizer AlPcS2a.