BIODISTRIBUTION OF I-125 AND IN-111 LABELED OV-TL 3 INTACT ANTIBODIES AND F(AB')2 FRAGMENTS IN TUMOR-BEARING ATHYMIC MICE

The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either In-111 or I-125. The highest tumor uptake was obtained with In-111-labeled intact OV-TL 3 (14,7% ID/g, 48 hr p.i.). For both antibody forms uptake of In-111 in liver, spleen and kidneys was very high. Furthermore, In-111 cleared more slowly from most tissues than I-125. As a result, tumor/tissue ratios with In-111-labeled OV-TL 3 were lower than with I-125-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with I-125-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. In-111-labeled OV-TL 3 F(ab')2 has already been shown to be a clinicaly useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using I-125-labeled OV-TL 3 F(ab')2.