THE EFFECT OF ANTIBODY PROTEIN DOSE OF ANTIRENAL CELL-CARCINOMA MONOCLONAL-ANTIBODIES IN NUDE-MICE WITH RENAL-CELL CARCINOMA XENOGRAFTS

BACKGROUND. Antibodies preferentially can direct radionuclides to soli d tumors. However, antibody uptake in tumors is often highly heterogen eous. This heterogeneity may be overcome by increasing antibody protei n dose. METHODS. The biodistribution of increasing protein doses of ra dioiodinated antirenal cell carcinoma (RCC) monoclonal antibodies (MoA bs) G250 and RC 38 was studied in mice with NU-12 or SK-RC-52 RCC xeno grafts. In addition, MoAb affinity constants and antigen densities (Sc atchard analysis) and MoAb processing (internalization) were determine d in vitro. RESULTS. The relative uptake of G250 in NU-12 tumors was v ery high at low protein doses (125% injected dose/g [%ID/g]), but decr eased at higher doses, suggesting tumor saturation. Indeed, saturation of G250 antigen occurred at 3 mu g protein. In this model, 9200 G250 determinants per NU-12 cell could be targeted, which is only 6.1% of t he 150,000 G250 determinants per NU-12 cell as determined in vitro. Th e RC 38 uptake in NU-12 tumors remained constant up to the 10 mu g dos e level (40% ID/g) and decreased at higher doses. RC 38 antigens were saturated at 25 mu g of RC 38. With RC 38, 15% of the available RC 38 antigens per NU-12 tumor cell were targeted. In contrast, G250 uptake in SK-RC-52 tumors was very low at low antibody dose (4% ID/g at 1 mu g) and increased with increasing protein dose. These differences in G2 50 biodistribution might be related to differences in the processing o f G250 by the tumor cells. CONCLUSIONS. Our studies show that some RCC tumors can be saturated with anti-RCC MoAbs at low (25 mu g) to very low (3 mu g) protein doses. At nonsaturated doses relatively high tumo r uptake can be achieved. Surprisingly in NU-12 tumors only 6.1% and 1 5% of the available antigenic sites were targeted at the saturating do se levels with G250 and RC 38, respectively. (C) 1997 American Cancer Society.