The antibody-linked chelating polymers for nuclear therapy and diagnostics.
This review deals with the problem of protein modification with chelating polymers. The main purpose of this approach is the preparation of monoclonal antibodies labeled with heavy metal isotopes (alpha-, beta-, and delta-emitting metals and metals used for NMR-tomography). Traditional binding of metals with proteins via chelating agents directly coupled to protein molecule does not allow binding a high number of metal atoms per single protein molecule and can also alter protein specific properties. At the same time, metal-to-protein binding via intermediate chelating polymer makes possible the binding of several dozen metal atoms per single protein without affecting its specific properties. Moreover, the variations in polymer properties and molecular weight allow controlled modified antibody biodistribution and clearance rate. Modified antibodies can be used successfully for nuclear and NMR diagnostics and for nuclear therapy. The following problems are discussed: the chemistry of the coupling of chelating groups to polymer backbone; the binding of chelating polymers to proteins, including monoclonal antibodies; the ability of chelating polymer-to-protein conjugates to bind heavy metals; the influence of the modification on protein conformation and specific properties; the behavior of metal-containing conjugates in vivo; the practical use of conjugates obtained for radioimmunoimaging, radioimmunotherapy, NMR-tomography, and in vitro immunoassays. Future prospects of the approach are also discussed.
Torchilin
V P
VP
Department of Enzyme Engineering, U.S.S.R. Cardiology Research Center, Moscow.
Klibanov
A L
AL
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002614:Chelating Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D009683:Nuclear Medicine / Q000379:methods*; D011108:Polymers / Q000138:chemical synthesis / Q000627:therapeutic use*; D011877:Radionuclide Imaging / Q000379:methods
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D011108:Polymers