The biodistributions of three 131I-labeled murine
monoclonal antibodies, NP-4 and Immu-14 anti(
carcinoembryonic antigen), and Mu-9 anti-(
colon-specific antigen p), were determined at antibody
protein doses varying from 1 microgram to 1000 micrograms in nude mice with small (0.1-0.4 g) GW-39 human
colonic cancer xenografts. For each antibody, the percentage of the injected dose per gram of
tumor and
tumor/nontumor ratios were constant over a wide
protein dose range. However, at high
protein doses (above 100 micrograms for NP-4 and Immu-14) the percentage of the injected dose per gram of
tumor and
tumor/nontumor ratios decreased. Assuming that the uptake of a control anti-(
alpha-fetoprotein) antibody represents the amount of antibody that accumulates in the
tumor nonspecifically (
i.e., antigen-independently), it could be shown that for each antibody the amount of antibody
protein that accumulates in the
tumor specifically, increases linearly with the
protein dose, reaching a plateau level at the highest doses tested. The growth inhibition of GW-39
tumor transplants in nude mice treated with 131I-labeled antibody at either low or high antibody
protein dose was compared. These experiments indicated that, in this experimental model, enhanced antibody
protein dose may decrease the therapeutic efficacy of radioiodinated
antibodies. It is suggested that heterogeneous distribution at low
protein dose, with intense localization around the blood vessels, may enhance the tumoricidal effect of radioantibodies.