title: Chelate radiochemistry: cleavable linkers lead to altered levels of radioactivity in the liver.
abstract: Bifunctional chelating agents based on benzyl-EDTA bind 111In stably under physiological conditions. Available evidence indicates that the indium is cleared from the body in its original chelated form. Initial studies of a series of antibody-chelate conjugates joined by different molecular linkers show that the 111In biodistribution is strongly dependent on the nature of the linker. Linkers containing thiourea, thioether, peptide, ester, and disulfide groups were compared in healthy BALB/c mice. The disulfide linker led to particularly rapid clearance of 111In from the liver, and from the whole body. Results did not appear to be as favorable as those currently obtainable with reversible radiolabelling techniques, in which the 111In chelate is bound non-covalently to the antibody and a competing hapten is used to displace it when desired. However, the concept of a metabolically cleavable linker is sound. Further exploration is needed to produce a conjugate with the desired properties.
authors.affiliation: Department of Chemistry, University of California, Davis 95616.
authors.forename: C F
authors.initials: CF
authors.lastname: Meares
authors.forename: M J
authors.initials: MJ
authors.lastname: McCall
authors.forename: S V
authors.initials: SV
authors.lastname: Deshpande
authors.forename: S J
authors.initials: SJ
authors.lastname: DeNardo
authors.forename: D A
authors.initials: DA
authors.lastname: Goodwin
mesh_terms: D000818:Animals; D002614:Chelating Agents; D004220:Disulfides; D007205:Indium Radioisotopes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D002614:Chelating Agents; D004220:Disulfides; D007205:Indium Radioisotopes