Quantification of Immunotoxin Number for Complete Therapeutic Response

Radiolabeled antibodies are commonly administered to patients, and their biodistribution to tumor and normal tissues is routinely quantitated by nuclear medicine scanning for dosimetry (1 ). Only a few studies have examined the uptake of radiolabeled immunotoxins into tumors or normal tissues (2 –7 ). These studies used toxin-ligand chemical conjugates and determined uptake by percentage of injected dose per gram of tissue (%id/g). The present review details the methods involved in determining the uptake of the recombinant immunotoxin LMB-2, and the calculations necessary to convert %id/g to the number of molecules binding specifically to each tumor cell. These methods can also be used for any radiolabeled ligand, including monoclonal antibodies (MAbs), to determine numbers of molecules per cell that bind to the target antigen in vivo. With immunotoxins, however, one can compare the number of molecules per cell needed for complete tumor regression with the need for eradication of tumor cells in monolayer culture.