Comparison of monoclonal antibody delivery to intracranial glioma xenografts by intravenous and intracarotid administration.
Monoclonal antibody 81C6, which is directed against a human gliomamesenchymal extracellular matrix antigen, was used to evaluate the potential advantage of intracarotid (i.c.) administration versus i.v. delivery to D-54 MG human glioma intracranial xenografts in immunosuppressed rats. Two approaches were taken. In paired-label analysis, 125I-labeled 81C6 and 131I-labeled isotype control antibody were given to separate groups of animals by either the i.v. or i.c. route. Biodistribution measurements as a function of time were analyzed in terms of the percentage of injected dose/g of tissue and localization indices. No significant difference (P greater than 0.19 to P greater than 0.56) was demonstrated between the i.v. and i.c. routes. To control for the large localization variation inherent in the animal model used, an alternative experimental design, paired-injection analysis, was performed in which 125I- and 131I-labeled 81C6 were simultaneously administered by the i.c. and i.v. routes to the same animal. Significantly higher levels of percentage of dose/g of tissue and localization ratios (P less than 0.05 to P less than 0.005) were shown from Day 1 to Day 3 for 81C6 given i.c. Approximately 20% more antibody was delivered to the D-54 MG intracranial tumor by the i.c. route during the experimental period of 5 days. No difference in the levels of normal tissue exposure between the two routes of administration was seen. These data suggest an advantage exists for whole monoclonal antibody given i.c. and that, theoretically, a greater advantage may be present for smaller molecules such as Fab and F(ab')2 fragments.
Lee, YS; Bullard, DE; Wikstrand, CJ; Zalutsky, MR; Muhlbaier, LH; Bigner, DD
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