A NEW MODEL OF RADIATION-INDUCED MYELOPATHY - A COMPARISON OF THE RESPONSE OF MATURE AND IMMATURE PIGS

Purpose: The development of an experimental model of radiation-induced myelopathy in the pig which would facilitate the study of the effects of clinically relevant treatment volumes. Methods and Materials: The effects of local spinal cord irradiation, to a standard 10 X 5 cm fiel d, have been evaluated in mature (37-42.5 weeks) and immature (15.5-23 weeks) pigs. Irradiation was with single doses of Co-60 gamma-rays at a dose-rate of 0.21-0.65 Gy/min. The incidence of paralysis was used as an endpoint. Results: Irradiation of mature animals resulted in the development of frank paralysis with animals showing combined parenchy mal and vascular pathologic changes in their white matter. These lesio ns, in common with those seen in patients, had a clear evidence of an inflammatory component. The latency for paralysis was short, 7.5-16.5 weeks, but within the wide range reported for patients. However, it wa s shorter than that reported in other large animal models. The ED(50) value (+/- SE) for paralysis was 27.02 +/- 0.36 Gy, similar to that in rats taking into account dose-rate factors. The irradiation of immatu re pigs only resulted in transient neurological changes after doses co mparable to those used in the mature animals, ED(50) value (+/- SE) 26 .09 +/- 0.37 Gy. The reasons for these transient neurological symptoms are uncertain. Conclusion: A reliable experimental model of radiation -induced myelopathy has been developed for mature pigs. This model is suitable for the study of clinically relevant volume effects.