29th Annual Meeting of the American Society of Photobiology

Downtown Marriot

Chicago, Il.

ALA Photodynamic Therapy: from Barrett's to Brain

Abstract-
Two separate studies are reported to evaluate the use of aminolevulinic acid (ALA) for photodynamic therapy of Barrett's esophagus or of malignant brain tumors. In the first, in 18 patients with Barrett's metaplasia, ALA was administered orally at 2, 10 or 30 mg/kg and at 1,3 or 6 h later fluorescence endoscopy (Xillix LIFE-GI system) and fluorescence point spectroscopy were performed in both Barrett's and normal regions. Biopsies were taken and split into 3 for histopathology, PpIX concentration by spectrofluorimetry, and confocal fluorescence microscopy. The Barrett's-to-normal squamous ratio was highest at low ALA dose but close to unity at 10 and 30 mg/kg. The pattern of PpIX microdistribution showed significant dose- and time-dependent features. The PpIX concentration was highly variable within the Barrett's epithelium: in particular there were biopsies in which deep-lying glands had little or no PpIX, suggesting that ALA-PDT may not be able to achieve full thickness mucosal ablation. Strategies to overcome or reduce this potential limitation are considered. In the second study, the uptake/ distribution and PDT effect of ALA-PpIX in malignant brain tumors and normal brain tissue was examined in animal models (rabbit, rat) and compared to several other PDT photosensitizers, in order to assess the potential for effective treatment of intracranial tumors and collateral damage to normal brain. PDT was given interstitially with an optical fiber placed into either tumor or normal brain. At appropriate times thereafter, the whole brain was excised and sectioned, and confocal microscopy used to map both the induced necrosis and apoptosis (by TUNEL assay). The necrosis in all tissues showed a threshold behavior, while apoptosis appeared stochastic in nature. In contrast to other photosensitizers, ALA-PpIX had no measurable necrotic effect on normal white matter. This makes it a particularly attractive candidate for PDT treatment of malignant brain tumors in adults. Fluorescence imaging in vivo using a purpose-built, long working-distance camera has also been implemented clinically during PDT (with Photofrin) and issues in applying this with ALA-PpIX imaging are considered in terms of both PDT monitoring and general surgical guidance.

Keywords: ALA-PDT, brain tumors, Barrett's esophagus, fluorescence