CUTANEOMUSCULAR RADIATION-INDUCED FIBROSI S (III) - MAJOR EFFICACY OFLIPOSOMAL SUPEROXIDE-DISMUTASE

Sub-cutaneous and muscular fibrosis are common and irreversible late e ffect of radiation on normal tissues. An experiment was designed to te st the effectiveness of superoxide dismutase in reducing late radiatio n injury. This study was performed in an experimental porcine model of acute localized gamma irradiation simulating human accidental overexp osure: 12 Large White pigs were irradiated on the thigh with a collima ted gamma Ir-192 source, so that the dose was 160 Gy/skin (100%) and 4 0 Gy/2 cm depth (25%). In this model, fibrosis appears in 4 to 5 month s. The heterogenous sclerotic tissue is composed of stable fibrotic ar eas poorly cellularized and active areas with a high density of myofib roblasts and inflammatory perifibrotic part. Lipsod administration mod alities were six intramuscular injections during 3 weeks (twice weekly ) either 10 mg/inj (five pigs) or of 100 mg/inj (five pigs). A methodi c evaluation by two examiners consisted of measurements being taken be fore and after treatment: sum of the two largest perpendicular measura ble dimensions, cutaneous projected surface of palpated fibrotic block , ultrasound fibrosis deepness and extrapolated volume. We conclude th at Lipsod is the first drug ever described that reduces radiation-indu ced fibrosis. Its efficacy in this model was highly significant, with a regression higher than 40% in size and 70% in surface and volume, 12 weeks after the end of treatment. This response was rapid, reproducib le without dose-effect or toxicity in the limits studied. This work co nfirms previously published results in humans.