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Abstract
During photodynamic therapy (PDT) both normal and pathological brain tissue, in close proximity to the light source, can experience significant temperature increases. The purpose of this study was to investigate the anti-tumor effects of concurrent 5-aminolevulinic acid (ALA)-mediated PDT and hyperthermia (HT) in human and rat glioma spheroids. Human or rat glioma spheroids were subjected to PDT, HT, or a combination of the two treatments. Therapies were given concurrently to simulate the conditions that will occur during patient PDT. Predictions of diffusion theory suggest that brain tissue immediately adjacent to a spherical light applicator may experience temperature increases approaching 8 degrees C for laser input powers of 2 W. In the in vitro model employed here, HT had no effect on spheroid survival at temperatures below 49 degrees C, while sub-threshold fluence PDT results in only modest decrease in survival. HT (40-46 degrees C) and PDT interact in a synergistic manner if the two treatments are given concurrently. The degree of synergism increases with increasing temperature and light fluence. Apoptosis is the primary mode of cell death following both low-fluence rate PDT and combined HT + PDT.
Highlights
Primary brain tumors are neoplasms that originate from the parenchymal elements of the brain
A simple diffusion model was used to predict the thermal distribution in brain tissues during photodynamic therapy (PDT) with a spherical light applicator
Theoretical calculations indicate that significant temperature increases are likely to occur in brain tissue immediately adjacent to a spherical light applicator following even modest input laser powers (Figure 1)
Summary
Primary brain tumors are neoplasms that originate from the parenchymal elements of the brain. There are approximately 17,000 new cases of primary brain tumors diagnosed within the United States every year and an equal number in the EU region [1]. Viable tumor cells can be demonstrated in biopsy material remote from the primary tumor site, failure of treatment is usually due to local recurrence at the site of surgical resection [2]. This would indicate that not curative, a more aggressive local therapy could be of benefit in prolonging patient survival and quality of life. Intracavity therapy offers the possibility of applying various treatment modalities (brachy, photodynamic and thermal therapies) aimed at the nests of tumor cells left in the resection border while minimizing damage to normal tissue [3,4,5]
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