Kinetics of interstitially administered monoclonal antibodies for purposes of lymphoscintigraphy

Abstract

The clearance rates of radiolabeled murine monoclonal intact IgG, F(ab')2 Fab and of an IgM following subcutaneous administration were evaluated in normal mice and rats using nuclear imaging and counting techniques. These studies suggest no significant difference in clearance rate exists between intact IgG and its F(ab')2 fragment, and little difference between these moieties and intact IgM. Fab is cleared considerably faster than the others, however. While significant differences in clearance rates exist, the magnitude of the differences are not as large as those following intravenous injection particularly when ambulation by the animal is allowed. When ambulation is allowed, clearance rates of all classes and fragments are accelerated and quite similar. Injection into the subcutaneous tissues of the footpad results in consistently faster clearance than an injection into the subcutaneous tissues of the abdomen. Ambulation considerably increased the clearance of antibodies, presumably by increasing lymph flow. These studies imply that the choice of intact antibody versus fragments for kinetic reasons may be less critical (particularly if ambulation is allowed) by the subcutaneous as compared with the intravenous delivery route. This kinetic information should be useful in designing imaging protocols with radiolabeled antibodies administered subcutaneously for purposes of imaging disease processes involving the lymphatics.