title: Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.
abstract: To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than 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 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.
authors.affiliation: Division of Nuclear Medicine, Cantonal Hospital and University Medical Center, Geneva, Switzerland.
authors.forename: J E
authors.initials: JE
authors.lastname: Ryser
authors.forename: K
authors.initials: K
authors.lastname: Rose
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Pelegrin
authors.forename: A
authors.initials: A
authors.lastname: Donath
authors.forename: R
authors.initials: R
authors.lastname: Egeli
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: R E
authors.initials: RE
authors.lastname: Offord
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D002614:Chelating Agents; D003110:Colonic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D003676:Deferoxamine / Q000494:pharmacology*; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D016719:Radioimmunodetection; D016499:Radioimmunotherapy; D014018:Tissue Distribution / Q000187:drug effects; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D005710:Gallium Radioisotopes; D007140:Immunoglobulin Fab Fragments; D003676:Deferoxamine