Radiolabeling of the antibody IgG M75 for epitope of human carbonic anhydrase IX by 61Cu and 64Cu and its biological testing

Appl Radiat Isot. 2019 Jan:143:87-97. doi: 10.1016/j.apradiso.2018.10.021. Epub 2018 Oct 25.

Abstract

Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells, while copper radioisotopes offer wide range of diagnostic, therapeutic and theranostic properties. The work was focused on a new approach to the labelling of antibody IgG M75 for epitope human carbonic anhydrase IX with copper radioisotopes 61Cu and 64Cu and its in vivo testing in mice with inoculated colorectal cancer. Monoclonal antibody IgG M75 for epitope human carbonic anhydrase IX was successfully conjugated with copper-specific chelator "phosphinate" and labelled with 61Cu and 64Cu The obtained molecule has considerable potential as a radioimmuno pharmaceutical suitable for imaging of tumours expressing carbonic anhydrase IX by positron emission tomography (PET).

Keywords: Carbonic anhydrase IX; Cu-61; Cu-64; PET; Tumour diagnostics; “phosphinate”.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antigens, Neoplasm / immunology*
  • Carbonic Anhydrase IX / immunology*
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / enzymology
  • Copper Radioisotopes / chemistry*
  • Copper Radioisotopes / pharmacokinetics
  • HT29 Cells
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacokinetics
  • Immunoglobulin G / chemistry
  • Male
  • Mice
  • Mice, Nude
  • Positron-Emission Tomography
  • Radioimmunodetection
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Copper Radioisotopes
  • Copper-61
  • Copper-64
  • Immunoconjugates
  • Immunoglobulin G
  • M75 monoclonal antibody
  • Radiopharmaceuticals
  • CA9 protein, human
  • Carbonic Anhydrase IX