[Distribution of ACNU in the rat brain after intracisternal injection--macroscopical autoradiographic study]

Abstract

In the previous reports, we demonstrated that intracisternal ACNU is effective in prolonging the survival time of rats with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, and systemic and local toxicity can be avoided by adjusting the drug dose. In this experiment, we studied distribution of 14C-ACNU in the rat brain after intracisternal administration using a macroscopical autoradiographic method. One muCi of ethylene-14C-ACNU was percutaneously injected into the cisterna magna of normal female Wistar rats weighing approximately 150 g. The animals were sacrificed 5 and 30 minutes, and 3 hours after injection (3 animals in each group). The brain was quickly removed and frozen in Freon. 14C-ACNU autoradiograms were made in coronal sections of the brain, which were cut in 20 mu thick and exposed to the film for 7 days. In 5 minutes after administration, high radioactivity was distributed in the subarachnoid space of the basal and ambient cisterns and hypocampal fissures, and subpial brain tissue up to 1 or 2 mm in depth. High radioactivity was also present in the ventricles and subependymal layer. In 30 minutes after administration, total radioactivity has already reduced in amount, however, local distribution has not changed so much as compared to that of 5 minutes after injection. No radioactivity was observed in the deeper part of the brain. In 3 hours after administration, only a small amount of radioactivity remained in the subarachnoid space and subpial region.(ABSTRACT TRUNCATED AT 250 WORDS)