Accessibility of circulating immunoglobulin G to the extravascular compartment of solid rat tumors.
We have measured the rate of influx (kin) of normal rat immunoglobulin G (IgG) from the blood into the fluid surrounding the cells of three syngeneic rat fibrosarcomas as well as rat skin, muscle, lung, and kidney. Also measured was the rate of efflux (kout) of IgG from the tumor and tissue back into the circulation. The value of kin ranged from 0.11 to 9.0% of the blood value (activity/ml blood) transferred/hr/g for the nonmalignant tissues and from 6.2 to 7.9% of the blood value transferred/hr/g for the three tumors. Dividing kin by the plasma volume of the tissue gave a measure of the permeability of the vascular bed of that tissue. This ratio was rather constant for the normal tissues studied; however, it was at least an order of magnitude larger in all three tumors, indicating that the vasculature of the tumors was very permeable to IgG. The interstitial fluid volume (IF) of the tumor and tissue was calculated. The IF of the three tumors contained approximately 0.5 ml of fluid per g, while the IF of normal tissues had values that ranged from 0.14 to 0.34 ml of fluid per g. Knowledge of the IF, kin, and kout allowed a calculation of the concentration of IgG in the fluid surrounding the cells of tumors and tissues. The concentration of IgG in the IF of the tumors was found to be 50% of the plasma concentration; this was larger than the concentration of IgG in the IF of normal tissues, where the values ranged from 9 to 28% of the plasma concentration. A model for Ab localization onto solid tumors was developed. The model was used to discuss the mechanism of localization as well as the physiological limits of drug- or isotope-coupled Ab localization.