RADIOPROTECTIVE EFFECTS OF THE 21-AMINOSTEROID U-74389G FOR STEREOTAXIC RADIOSURGERY

OBJECTIVE: Future improvements in the results of stereotactic radiosur gery will be related to better patient selection, dose planning, radio sensitization of the target, and, possibly, protection of the brain su rrounding the target. 21-Aminosteroids may provide protection against brain radiation injury by inhibition of lipid peroxidation and a selec tive action on vascular endothelium. We hypothesized that the 21-amino steroid U-74389G would reduce radiosurgery-related brain injury withou t attenuating the target volume response. METHODS: One hundred and for ty-five rats were divided into four experimental groups before undergo ing radiosurgery: control (n = 47); low-dose U74389C (5 mg/kg of body weight, n = 30); high-dose U-74389G (15 mg/kg, n = 20); and methylpred nisolone (2 mg/kg, n = 48). The drug was administered 1 hour before ra diosurgery (4-mm gamma knife collimator) of the normal rat frontal lob e (single-fraction maximum doses of 50, 100, or 150 Gy) was performed. All brains underwent histological examination at 90 or 150 days to ev aluate the diameter of necrosis and the findings of radiation-induced vasculopathy, brain edema, and gliosis. RESULTS: None of the animals t hat received 50-Gy radiation developed histological changes, whereas a ll of the animals that received 150-Gy radiation developed radiation n ecrosis without drug-induced protection from vascular changes or edema . In animals receiving 100-Gy radiation, high-dose aminosteroid reduce d radiation-induced vasculopathy at 90 days (P = 0.06) and at 150 days (P = 0.02) and prevented regional edema at 90 days (P = 0.01) and at 150 days (P = 0.03). Low-dose aminosteroid and corticosteroid provided no protection. CONCLUSION: The 21-aminosteroid U-74389G provided prot ection after a single intravenously administered dose of 15 mg/kg agai nst radiation-induced vasculopathy and edema. High-dose 21-aminosteroi ds seem to have optimal properties for radiosurgery, surrounding brain protection without reducing the therapeutic effect desired within the target volume.