THE EFFECT OF HYPOTHERMIA AND HYPERTHERMIA ON PHOTODYNAMIC THERAPY OFNORMAL BRAIN

THE EFFECT OF whole body hyperthermia and hypothermia in conjunction w ith photodynamic therapy (PDT) was determined on normal rat brain. Hyp erthermia animals (Group I, n = 18) were warmed until their core body temperature reached 40 degrees C, (brain temperature, 39.7 +/- 0.5 deg rees C) and maintained at 40 +/- 1 degrees C for 30 minutes prior to a nd after PDT. Hypothermia (Group II, n = 31) animals were cooled to 30 +/- 1 degrees C (brain temperature, 29.3 +/- 0.4 degrees C) for 1 hou r. PDT treatment was performed, and the body temperature of the animal s was maintained at 30 degrees C for 2 hours post-PDT. A population of animals was subjected to PDT under normothermic (Group III, n = 16; b ody temperature, 37 +/- 1 degrees C; brain temperature, 36.7 +/- 0.8 d egrees C) conditions and treated in a manner identical to that of hype rthermic animals. PDT was performed with 17 J/cm(2), 35 J/cm(2) or 70 J/cm(2) (100 mW/cm(2)). Photofrin (Quad- ralogic Technologies Ltd., Va ncouver, Canada) (12.5 mg/kg) was injected intraperitoneally 48 hours prior to laser treatment on all three groups. Wet-dry weight measureme nts were obtained on a separate set of all three groups of animals (n = 27). Cortical lesion depths were measured, and pathological evaluati on was made at 24 hours post-PDT. No difference in the wet-dry weight measurements or histopathology was present between the th ree groups o f animals. Lesion depths for Group I animals did not significantly dif fer from Group III animals. However, lesion depths in Group II animals at 17, 35, and 70 J/cm(2) were significantly less than those for Grou p III animals at these energy levels. These results suggest that in vi vo, mild hyperthermia does not influence normal brain PDT damage and t hat hypothermia may reduce damage to normal brain from PDT.