The Effect of Hypothermia and Hyperthermia on Photodynamic Therapy of Normal Brain

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Abstract
THE EFFECT OF whole body hyperthermia and hypothermia in conjunction with photodynamic therapy (PDT) was determined on normal rat brain. Hyperthermia animals (Group I, n = 18) were warmed until their core body temperature reached 40° C, (brain temperature, 39.7 ± 0.5° C) and maintained at 40 ± 1° C for 30 minutes prior to and after PDT. Hypothermia (Group II, n = 31) animals were cooled to 30 ± 1° C (brain temperature, 29.3 ± 0.4° C) for 1 hour. PDT treatment was performed, and the body temperature of the animals was maintained at 30° C for 2 hours post-PDT. A population of animals was subjected to PDT under normothermic (Group III, n = 16; body temperature, 37 ± 1°C; brain temperature, 36.7 ± 0.8° C) conditions and treated in a manner identical to that of hyperthermic animals. PDT was performed with 17 J/cm2, 35 J/cm2, or 70 J/cm2 (100 mW/cm2). Photofrin (Quadralogic Technologies Ltd., Vancouver, Canada) (12.5 mg/kg) was injected intraperitoneally 48 hours prior to laser treatment on all three groups. Wet-dry weight measurements were obtained on a separate set of all three groups of animals (n = 27). Cortical lesion depths were measured, and pathological evaluation was made at 24 hours post-PDT. No difference in the wet-dry weight measurements or histopathology was present between the three groups of animals. Lesion depths for Group I animals did not significantly differ from Group III animals. However, lesion depths in Group II animals at 17, 35, and 70 J/cm2 were significantly less than those for Group III animals at these energy levels. These results suggest that in vivo, mild hyperthermia does not influence normal brain PDT damage and that hypothermia may reduce damage to normal brain from PDT.