ELIMINATION OF FREE RADIONUCLIDE BY A CHELATING AGENT IMPROVES TUMOR-TO-NONTUMOR RATIOS FOLLOWING RADIOIMMUNOTARGETING WITH ANTIBODY LABELED WITH GA-67

To circumvent radionuclide accumulation in nontarget tissues when empl oying metallic radionuclides for radioimmunoscintigraphy or radioimmun otherapy, we have investigated the effect of the chelating agent defer roxamine (DFO) on the biodistribution of Ga-67 following its administr ation attached to intact monoclonal antibody MAb35 and its F(ab')(2) f ragment. Following administration of Ga-67-labeled MAb35, DFO accelera ted whole-body elimination of Ga-67 and reduced its accumulation in se veral normal tissues, including liver, spleen and kidney, No reduction in tumor accumulation of Ga-67 was observed, Following administration of Ga-67-labeled F(ab')(2) fragment, kidney accumulation was higher t han with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of Ga-67 was seen following DFO, although liver, kidney and blood levels were reduced and whole body elimination accel erated. (C) 1998 Elsevier Science Inc.