DEXAMETHASONE DECREASES THE DELIVERY OF TUMOR-SPECIFIC MONOCLONAL-ANTIBODY TO BOTH INTRACEREBRAL AND SUBCUTANEOUS TUMOR XENOGRAFTS

THE EFFECT OF dexamethasone on the delivery of monoclonal antibody L6 IgG to intracerebral and subcutaneous LX-1 small cell lung carcinoma x enografts was evaluated in nude rats (n = 157). Dexamethasone (0, 8, o r 24 mg/m2) was given 18 hours before infusion of L6 IgG, with or with out osmotic disruption of the blood-brain barrier. Compared with contr ols, the 8 mg/m2 dose decreased delivery of L6 IgG (12-37%) to all tis sues, but the only significant decrease (P < 0.001) was in the subcuta neous tumor (37%). In the 24 mg/m2 group, L6 IgG delivery was signific antly (P < 0.001) decreased to all tissues (37-60%). Dexamethasone had no effect on plasma levels. Barrier disruption significantly (P < 0.0 001) increased L6 IgG delivery to intracranial tumor and surrounding b rain, but not to subcutaneous tumor or plasma. The percentage of decre mental effect of dexamethasone on L6 IgG delivery was the same with an d without barrier disruption and was not associated with the time the animals were killed (P > 0.05). Compared with controls, the ratio of i ntracranial tumor to normal brain showed no change with dexamethasone, but the ratios of both intracranial and subcutaneous tumors to plasma significantly (P < 0.002) decreased with both doses. The in vitro cel l binding capacity of L6 IgG to LX-1 cells remained unchanged after in cubation of cells with dexamethasone over a 3-log concentration for 4 days, demonstrating no effect on antigen expression. This study sugges ts that dexamethasone has a clinically relevant generalized (i.e., cen tral nervous system and systemic) vascular effect on permeability to L 6 IgG monoclonal antibody.