Delivery of Melanoma-associated Immunoglobulin Monoclonal Antibody and Fab Fragments to Normal Brain Utilizing Osmotic Blood-Brain Barrier Disruption
作者： Edward A. Neuwelt , Peggy A. Barnett , Christopher I. McCormick , I. Hellström , Paul Beaumier
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摘要: Iodinated monoclonal antibodies (IgG 96.5 and two monomeric Fab fragments 48.7) to melanoma-associated antigens were administered after osmotic blood-brain barrier (BBB) opening in normal rats. Osmotic BBB disruption significantly ( P <0.0001) increased antibody delivery the brain. Following intracarotid administration, there was no difference disrupted brain concentration integral area under curve between IgG over 72-h experimental period. However, initially higher than IgG, clearance more rapid < 0.001), decreasing 50% by approximately 4.5 h compared 25.5 for IgG. Plasma also The levels decreased 1.5 15 route timing of infusion had a significant effect on with but not intact Antibody recovered from retained its immunological reactivity as measured cell binding assay at least 24 h. ipsilateral 0.001) increasing dose 3-log range. These data provide information applicable therapeutic use tumor treatment.
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