COMPARISON OF THE BIODISTRIBUTION AND THE EFFICACY OF MONOCLONAL-ANTIBODY 323 A3 LABELED WITH EITHER I-131 OR RE-186 IN HUMAN OVARIAN-CANCER XENOGRAFTS/

Purpose: The radionuclide Re-186 has favorable physical characteristic s for use in radioimmunotherapy, including the emission of beta-partic les of a high energy and a low-abundance of gamma-emission, The gamma- emission, in particular, is ideal for tumor imaging and poses less haz ards to the patient and the medical personnel when compared with the g amma-emission of the widely used radionuclide I-131, In the present st udy, we determined whether Re-186-labeled monoclonal antibody 323/A3 m ay be better suited for the treatment of ovarian cancer than I-131-323 /A3. Methods and Materials: We compared the biodistribution and the ef ficacy of Re-186- and I-131-labeled 323/A3 in nude mice bearing s.c. t he human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. Re-186 was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltrigly cine (S-benzoyl-MAG3) chelate. Results: A molar ratio of Re-MAG3:323/A 3 of 3:1 did not affect the integrity and the pharmacokinetic behaviou r of the MAb, The tumor uptake and the retention of Re-186- and I-131- labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by Re-186-323/A3 was 1.3-fold higher than that of I-131-323/A3, When mice were treated with equivalent radionucl ide doses, the tumor growth inhibition induced by Re-186-323/A3 was si milar or slightly better when compared with the efficacy of I-131-323/ A3, When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for b oth conjugates, I-131-323/A3 was slightly more effective in the inhibi tion of the growth of FMa and OVCAR-3 xenografts. Conclusions: The fav orable physical characteristics of Re-186 as well as its efficacy when conjugated to a MAb indicate Re-186 as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients, (C) 1997 Elsevier Scien ce Inc.