WR-2721 entry into the brain across a modified blood-brain barrier.

摘要: Radioprotection of the CNS by WR-2721 has not been possible because its inability to cross blood-brain barrier (BBB) and so gain access neural tissue. Modification BBB using hypertonic arabinose (1.8 m), injected via internal carotid artery (ica), permitted entry ip-injected (/sup 14/C)WR-2721 into ipsilateral cerebral hemisphere. The BBB-modified hemisphere had a 5.34-fold increased uptake compared nonmodified controls. Delivery as bolus ica further enhanced after opening; was 3.73 times greater than ip injection. A 20-fold increase brain calculated for administration with opened route without modification. Toxicity ip-administered open only 1.4 non-modified controls 1.96 more toxic when delivered ica. These data demonstrate significant CNS, previously unprotected organ, provide model future radioprotective studies.