Minimally Invasive Photodynamic Therapy (PDT) for Ablation of Experimental Rat Glioma

Abstract

The feasibility of using ALA-mediated photodynamic therapy (PDT) tumor ablation as a minimally invasive treatment alternative for malignant brain tumors was evaluated in a rodent model. Treatment efficacy and side effects were evaluated with MRI, histopathology and survival rates. BT (4)C orthotopic brain tumors were induced in BD-IX rats. At various time intervals following tumor induction the animals were given 5-aminolevulinic acid (ALA) and 4 hours later optical fibers were inserted directly into the tumor without mechanical debulking or cranial decompression. A 3-day course of steroid treatment was initiated immediately prior to PDT. All untreated animals inevitably died within one month after tumor implantation (28.5 +/- 2.5 days). Complete tumor eradication was achieved in only 1/17 rats, but a significant increase in survival was obtained in the group of animals receiving 125 mg/kg ALA and 26 Joules of light fluence. Histopathology revealed large areas of central tumor necrosis, although clusters of viable tumor cells were often found at the tumor periphery. Pronounced edema in the necrotic tumor center as well as in the surrounding brain, and along white matter tracts was evident in all the brains studied from PDT-treated animal. This study suggests that ALA-mediated PDT may become a promising alternative therapy for the minimally invasive treatment of brain tumors. A judicious choice of PDT regimens that minimizes inflammatory responses through the use multiple fractionated long-term treatment protocols would likely be required.