Preparation and preclinical assessment of folate-conjugated, radiolabelled antibodies.

نویسندگان

  • Gjermund Henriksen
  • Oyvind S Bruland
  • Roy H Larsen
چکیده

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.

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عنوان ژورنال:
  • Anticancer research

دوره 25 1A  شماره 

صفحات  -

تاریخ انتشار 2005