Damage Threshold of Normal Rat Brain in Photodynamic Therapy

Abstract

Normal brain tissue response to photodynamic therapy (PDT) must be quantified in order to implement PDT as a treatment of brain neoplasm. We therefore calculated the threshold for PDT-induced tissue necrosis in normal brain using Photofrin (porfimer sodium, Quadralogic Technologies Inc., Vancouver, BC) as the photosensitizer. The absolute light fluence-rate distribution for superficial irradiation and effective attenuation depth were measured in vivo using an invasive optical probe. Photosensitizer uptake in cerebral cortex was measured with chemical extraction and fluorometric analysis. Photodynamic therapy-induced lesion depths at various drug dose levels were measured as a biological end point. The PDT threshold for normal brain necrosis was calculated as in the magnitude of 10(16) photons/cm3. Thus normal rat brain is extremely vulnerable to PDT damage. This suggests that extra precautions must be exercised when PDT is used in brain.

Spatial Laser Induced Fluorescence Imaging (SLIFIMG) Analysis to Assess Tissue Photosensitizer Uptake

“…The uptake and retention of i.v. administered photosensitizer by tumor tissue is one of several fundamental determinants of the clinical effectiveness of PDT as mentioned by Weersink, R. A., et al, 1997, Chen, Q., et al., 1996, Love, W. G., et al, 1996 and Windahl, T., et al, 1993 which comply with our obtained results that study of PS tissue uptake reflects many aspects that facilitate the understanding and how we can optimally benefit from this useful treatment modality [17][18][19][20]. Using Matlab to study and analyze tissue auto fluorescence was applied by Kamath SD and Mahato KK 2007 the demonstrated that Matlab is a good tool for the spectral analysis and classification for discrimination of autofluorescence spectra of pathologically certified normal, premalignant, and malignant oral tissues [21].…”

Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5‐aminolevulinic acid induced protoporphyrin IX

“…Unselective effects of HpD and Photofrin1 were also described in animal studies [12,[33][34][35][36][37] and have been related to both the inhomogeneous distribution of the PS within the tumors and extensive leakage of the PS to the surrounding normal tissue (via peritumoral edema bulk flow). PDT by means of 5-ALA induced PPIX is expected to induce less often and less severe side effects for several reasons: (1) The drug applied systemically (5-ALA) is itself not phototoxic, (2) 5-ALA induced PPIX has been shown to accumulate selectively within the tumor, and (3) a significant redistribution of the PS by peritumoral edema bulk flow does not seem to occur.…”

A Telemetric light delivery system for metronomic photodynamic therapy (mPDT) in rats

“…However, brain tissue is extremely sensitive to immune responses caused by tumor cell necrosis [14]. It therefore has been suggested that PDT with a light dose below the necrotic threshold of brain tissue [18] administered during an extended time period can lead to selective apoptosis of tumor cells that have remained in the brain after surgical resection. This approach has been called mPDT and is under investigation by a number of centers [19][20][21][22].…”