TUMOR RETENTION OF RE-186-MAG3, IN-111-DTPA AND I-125 LABELED MONOCLONAL-ANTIBODY G250 IN NUDE-MICE WITH RENAL-CELL CARCINOMA XENOGRAFTS

In radioimmunotherapy of solid tumors substantial gain might be achiev ed by carefully selecting the radionuclide and the linker connecting i t to the antibody In contrast to I-131, radiometals such as Y-90 and I n-111 may be retained in the tumor cell after internalization of the a ntibody, thereby enhancing the radiation dose to the tumor, The physic al properties of Re-186 with 1.08 MeV beta-emission (71%) and 137 keV gamma-emission (10%) seem ideal for radioimmunotherapy. In this study we investigated in nude mice with s. c. renal cell carcinoma xenograft s the biodistribution and the retention in the tumor of Re-186-MAG3 la beled monoclonal antibody (mAb) G250 as compared to In-111-DTPA-G250, to I-125-G250 and to I-131-MN14 (non-specific control mAb). Radiolabel ed antibody preparations were i.v. injected. Seventy two hours p.i. th e biodistribution of the radiolabel was determined. Blood levels of al l mAb G250 preparations were remarkably low (mean: 2.38, 1.40 and 1.43 %ID/g for I-125, In-111 and Re-186 respectively) whereas blood levels of mAb MN14 were significantly higher (mean: 12.3 %ID/g), indicating tumor processing of mAb G250. Retention of In-111 in the tumor was sig nificantly higher than of Re-186 and I-125 whereas retention in the tu mor of Re-186 and I-125 did not differ significantly. Conclusion: In c ontrast to other radiometals such as In-111 and Y-90, Re-186 is not re tained in the tumor cell. Therefore Re-186 has no additional advantage for radioimmunotherapy with respect to retention in the tumor.