title: Comparative biodistribution studies of DTPA-derivative bifunctional chelates for radiometal labeled monoclonal antibodies.
abstract: Biodistribution of five different backbone-substituted derivatives of SCN-Bz-DTPA (1B4M-DTPA, 1M3B-DTPA, 1B3M-DTPA, GEM-DTPA and 2B-DTPA) linked to MAb B72.3 were compared to that of the parent molecule after labeling with 111indium. Athymic mice, bearing human colon carcinoma xenografts (LS-174T) were injected i.v. to determine the biodistribution of the MAb chelate conjugates. Three of the MAb metal chelate conjugates (1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA), labeled with 111In showed efficient and stable tumor localization as well as a slower blood clearance rate than SCN-Bz-DTPA, GEM-DTPA or 2B-DTPA MAb chelate conjugates. Major differences were also seen in normal organ uptake, especially liver and spleen. Tumor-to-liver ratios rose as a function of time for 1B4M-DTPA, 1M3B-DTPA and 1B3M-DTPA MAb chelate conjugates with virtually no accumulation of the radiometal into this organ, as revealed by no increase in the liver-to-blood values. Small accretion in normal liver was noted for SCN-Bz-DTPA, GEM-DTPA or 2B-DTPA MAb chelate conjugates. The results reviewed here, and described previously (Roselli et al., 1991) demonstrate that the use in vivo of backbone-substituted forms of the SCN-Bz-DTPA, such as 1B4M-DTPA, 1M3B-DTPA, and 1B3M-DTPA bound to MAbs, can reduce uptake of indium to normal organs while maximizing the dose to tumor.
authors.affiliation: Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: M
authors.initials: M
authors.lastname: Roselli
authors.forename: J
authors.initials: J
authors.lastname: Schlom
authors.forename: O A
authors.initials: OA
authors.lastname: Gansow
authors.forename: M W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: S
authors.initials: S
authors.lastname: Mirzadeh
authors.forename: C G
authors.initials: CG
authors.lastname: Pippin
authors.forename: D E
authors.initials: DE
authors.lastname: Milenic
authors.forename: D
authors.initials: D
authors.lastname: Colcher
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D002614:Chelating Agents / Q000493:pharmacokinetics*; D003110:Colonic Neoplasms / Q000378:metabolism; D007205:Indium Radioisotopes; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007205:Indium Radioisotopes; D004369:Pentetic Acid