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

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 degrees C, (brain temperature, 39.7 +/- 0.5 degree C) and maintained at 40 +/- 1 degree C for 30 minutes prior to and after PDT. Hypothermia (Group II, n = 31) animals were cooled to 30 +/- 1 degree C (brain temperature, 29.3 +/- 0.4 degree C) for 1 hour. PDT treatment was performed, and the body temperature of the animals 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; body temperature, 37 +/- 1 degree C; brain temperature, 36.7 +/- 0.8 degree 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.(ABSTRACT TRUNCATED AT 250 WORDS)

ALA-PpIX mediated photodynamic therapy of malignant gliomas augmented by hypothermia

“…The mechanism may be similar to those from stroke like-models, whereby the volumes of inflammation and damage were reduced by half[ 48 , 49 ], albeit some studies did not employ corticosteroids. The data confirm and extend work by Dereski et al[ 21 ] who showed limited neuronal damage for Photofrin mediated hypothermia PDT, suggesting that the hypothermia effect is photosensitizer independent.…”

“…Our own in vitro study demonstrated that hypothermia (32–34°C) increased PpIX concentrations in glioma tumor cell lines, and improved FGR selectivity and the PDT therapeutic index [ 20 ]. Consistently, Dereski et al demonstrated a thermal induced PDT-responsivity shift of healthy brain leading to a change in the therapeutic index[ 21 ], whereby hypothermia demonstrated neuroprotective effects for vascular-acting Photofrin mediated PDT[ 21 ]. Mild hypothermia has been shown to protect neurons following various in vitro and in vivo stroke-like insults[ 22 ], following hypoxia or glucose deprivation[ 23 , 24 ] or acute neuronal injury[ 23 , 24 ].…”

Evaluation of a chloroaluminium phthalocyanine-loaded magnetic nanoemulsion as a drug delivery device to treat glioblastoma using hyperthermia and photodynamic therapy

“…29 Dereski et al found that the effects were greater than additive when HPT was given post-PDT. 34 Hyperthermic temperatures were found to inhibit repair of sub-lethal damage thereby making hypoxic cells more sensitive to PDT. Using a murine mammary adenocarcinoma model Chen et al showed that the combination of PDT and HPT produced a synergetic tumor response.…”

Addition of ionizing radiation or hyperthermia enhances PDT efficacy in glioma spheroids

“…The effects of HT and PDT have been investigated in a number of in vitro [6][7][8][9][10][11] and in vivo [12][13][14][15][16][17][18][19][20] systems. Variable effects have been reported following combined HT and PDT, with the degree and type of interaction dependent on a number of factors including tumor type, treatment sequence, time interval between treatments and photosensitizer type.…”