TIRILAZAD DOES NOT PROTECT RAT-BRAIN FROM BRACHYTHERAPY-INDUCED INJURY

BACKGROUND Acute and chronic brain injury are common sequelae of high- dose focused radiation, as in radiosurgery and brachytherapy. Developm ent of protectors of radiation injury, which would work in brain but n ot in tumor, would help enhance the therapeutic ratio of focused-radia tion therapy. METHODS Radiation protection by a clinically available 2 1-aminosteroid, Tirilazad, was studied in a rat brain brachytherapy mo del, both in tumor and non-tumor-bearing animals. For the tumor model, 9L Glioma/SF line cells were implanted stereotactically into the righ t frontal lobe of F-344 rats and grew to a sphere of 5.0-mm diameter a fter 12 days. Animals received a standard brachytherapy dose of 80 Gy to a 5.5-mm radius volume administered by a high-activity removable io dine-125 seed. Radiation damage was evaluated 24 hours after removal o f the seeds in all animals and again at 3 months in non-tumor-bearing animals, by T-1-weighted gadolinium-enhanced and T-2-weighted magnetic resonance imaging (MRI) on a 1.5-T unit. Treated animals received Tir ilazad 5 mg/kg intravenously 15 minutes prior to implant, 1 hour after implant, every 6 hours for the duration of the implant, and for 24 ho urs after removal of the seed. Control animals were administered vehic le only. RESULTS In both non-tumor-bearing and tumor-bearing rats, no difference in the volume of lesions on enhanced T-1 or T-2 MRI was see n between the Tirilazad-treated and control groups. In the non-tumor-b earing rats, volume of both T-1 enhancement and T-2 MRI lesions was si gnificantly reduced at 3 months compared to the values at 24 hours. CO NCLUSIONS In the present model, Tirilazad failed to reduce the volume of radiation brain injury from brachytherapy as seen on MRI, studied a cutely in tumor-bearing and non-tumor-bearing animals and also at 3 mo nths in non-tumor-bearing rats.