A comparative autoradiographic study demonstrating differential intratumor localization of monoclonal antibodies to cell surface (Lym-1) and intracellular (TNT-1) antigens.

Abstract

Autoradiography was utilized to explore the patterns of distribution of two different monoclonal antibodies (Lym-1 and TNT-1) in tumor-bearing nude mice. Lym-1 is an antibody against a cell surface B-cell antigen. In comparison, TNT-1 represents a novel approach and is an antibody against an intracellular (nuclear) antigen that is selectively revealed in degenerating tumor cells. Experimentally iodine-125-(125I) labeled Lym-1 or TNT-1 was injected intravenously into nude mice bearing either the Raji lymphoma or the ME-180 human cervical carcinoma. Qualitative autoradiographic analyses performed after injection revealed that Lym-1 accumulated at the periphery of the target tumor where vascular permeability is marked and where Lym-1 positive cells are first encountered. By contrast, TNT-1 lost its initial peripheral distribution and demonstrated progressive concentration in the center of the tumor where binding to its nuclear antigen is facilitated by the presence of cell degeneration and necrosis. These studies confirm the ability of TNT-1 to bind areas deep within tumor that traditionally are considered inaccessible to antibodies administered for imaging and therapy.