title: Direct stereotactic intracerebral injection of monoclonal antibodies and their fragments: a potential approach to brain tumor immunotherapy.
abstract: Delivery of monoclonal antibodies (Mab) to brain tumors is restricted by the blood:brain barrier. To circumvent this problem, we studied direct stereotactic injection of the Mab into the brain. An anti-melanoma intact Mab and its Fab fragments, which do not react with normal rat brain, were radioiodinated and injected either intracerebrally (IC) or intravenously (IV) into rats. At 5 days after injection, IC delivery of intact antibody was 101 times higher than IV delivery. The ratio of radioantibody in injected cerebrum:blood was 14:1. With IC delivered Fab fragments, the radioantibody ratio in injected cerebrum:blood was 242:1 at 5 days after IC injection, with a 680-fold delivery advantage over IV injection. These data demonstrate a dramatic regional delivery advantage for intact Mab and especially for Fab fragments injected directly into the brain. This route of Mab delivery may have therapeutic potential for brain tumors.
authors: Department of Surgery, University of Michigan, Ann Arbor 48109.
authors: M
authors: M
authors: Liebert
authors: R L
authors: RL
authors: Wahl
authors: G
authors: G
authors: Lawless
authors: P E
authors: PE
authors: McKeever
authors: J A
authors: JA
authors: Taren
authors: W H
authors: WH
authors: Beierwaltes
authors: R
authors: R
authors: Brasswell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007457:Iodine Radioisotopes; D008546:Melanoma, Experimental / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes