The role of the lymphatic system in the absorption and biodistribution of antitumor agents and monoclonal antibodies in normal and tumor-bearing mice is under investigation. Compared with intravenous administration, monoclonal antibodies given by subcutaneous injection are delivered with higher efficiency to regional lymph nodes where they bind specifically to lymphoid cells. Theoretical studies and large-scale pharmacokinetic studies in mice of both specific and nonspecific monoclonal antibodies, whole antibody and fragments, and several metabolites of iodinated antibodies have now been completed for both intravenous and subcutaneous routes of administration. The pharmacological principles that have emerged from studies in mice are being applied to the design of clinical protocols for the detection of melanoma, T-cell lymphoma, Hodgkin's disease, lung carcinoma and breast carcinoma. Conjugates of anti-B-cell antibody, coupled with an alpha--emitting radiometal bismuth-212, demonstrated specific cytotoxicity in vitro. However, these conjugates were not active in vivo against lymph node metastases of the guinea pig line 10 hepatoma which we attribute to poor immunoractivity and insufficient radiation dose.
