Anti-CEA monoclonal antibody: technetium-99m labeling and the validation process of a scintigraphic animal model with a non-cellular antigenic implant

Cell Mol Biol (Noisy-le-grand). 2002 Jul;48(5):511-6.

Abstract

Animal models are currently used to verify the biodistribution of different radiopharmaceuticals before its clinical application in Nuclear Medicine; however, there may be some limitations. The utilization of labelled anti-tumor monoclonal antibodies (MoAb) in experimental models often requires implant of human antigens (usually a cellular implant), which cannot be achieved in immunocompetent animals. Our purpose was to label an anti-CEA MoAb with technetium-99m (99Tc) and to validate a simplified animal model using a noncellular antigenic implant. MoAb was directly labelled with 99mTc, after reduction with 2-mercaptoethanol. Labeling efficiency was checked by ascending chromatography and immunoreactive fraction was measured in plastic wells sensitized with the antigen. Radiopharmaceutical biodistribution was evaluated by dissection and scintigraphy in 5 mice groups; following the subcutaneous administration of Al(OH)3, CEA adsorbed Al(OH)2 and a control group evaluation. Labeling efficiency was 94+/-3%, which showed to be stable for 24 hr, with immunoreactive fraction above 50%. Invasive biodistribution evaluation showed prolonged blood retention, hepatic and renal uptake. A significant increase in uptake was observed in scintigraphic studies of animals with CEA-adsorbed Al(OH)3 implants compared with the other groups (p<0.05). The non-cellular antigenic implant model simplifies the pre-clinical evaluation of labelled MoAb.

Publication types

  • Validation Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacokinetics*
  • Antibodies, Neoplasm / immunology
  • Carcinoembryonic Antigen / immunology*
  • Drug Evaluation, Preclinical
  • Immunoconjugates / administration & dosage
  • Immunoconjugates / pharmacokinetics
  • Male
  • Mice
  • Models, Animal
  • Organ Specificity
  • Radionuclide Imaging
  • Technetium* / administration & dosage
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Carcinoembryonic Antigen
  • Immunoconjugates
  • Technetium