Preparation and Preclinical Assessment of Folate-Conjugated, Radiolabelled Antibodies

Anticancer Res. Jan-Feb 2005;25(1A):9-15.


Background: The folate receptor (FR) is frequently over-expressed on human cancer cells and may be a suitable target for radiopharmaceuticals. Because of FR expression in the kidneys, the rapidly renal clearing folate is not well suited as a carrier for therapeutic radionuclides. As an alternative, folate-immunoglobulin conjugates were studied as potential carriers for radionuclides.

Materials and methods: Two types of conjugate were evaluated: (i) folate conjugated to osteosarcoma antigen directed murine monoclonal antibodies TP-1 and TP-3 or (ii) folate conjugated to non-specific polyclonal human IgG (HIg6). These constructs were labelled with 211At or 125I.

Results: The folate-HIg6-radionuclide conjugate showed high affinity to immobilized folate binding protein and also to folate receptor-expressing cells. Folate conjugates of TP-1 and TP-3 had a selective binding in vitro to antigen-expressing tumor cells and also to cells expressing FR only, thus the folate antibody constructs possessed dual affinity binding. Comparisons between folate-conjugated and non-folated antibody in Balb/C mice showed that the folate did not markedly change the properties of the radiolabelled antibody.

Conclusion: It was demonstrated that folate-conjugated antibodies carrying therapeutic radionuclides have relevant properties for the targeting of tumor cells expressing FR.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacokinetics
  • Antigens, Neoplasm / immunology
  • Astatine / chemistry
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Female
  • Folate Receptors, GPI-Anchored
  • Folic Acid / analogs & derivatives*
  • Folic Acid / pharmacokinetics
  • HeLa Cells
  • Humans
  • Immunoconjugates / chemistry*
  • Immunoconjugates / immunology
  • Immunoconjugates / pharmacokinetics
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Iodine Radioisotopes / chemistry*
  • Iodine Radioisotopes / pharmacokinetics
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Osteosarcoma / immunology
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / immunology
  • Radiopharmaceuticals / pharmacokinetics
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism
  • Tissue Distribution
  • Tritium / chemistry


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Carrier Proteins
  • Folate Receptors, GPI-Anchored
  • Immunoconjugates
  • Immunoglobulin G
  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Receptors, Cell Surface
  • Tritium
  • Folic Acid
  • Astatine