Preparation and Bioevaluation of 177Lu-labelled Anti-CD44 for Radioimmunotherapy of Colon Cancer
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CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrixinteractions. In particular, splice variants of CD44 are particularly overexpressed in a large numberof malignancies and carcinomas. In this study, the 177Lu-labelled CD44 targeting antibodywas prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with theequivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with 177Lu atroom temperature within 15 minutes. The stability was tested in human serum. An in vitro studywas carried out in HT-29 human colon cancer cell lines. For the biodistribution study 177Lu-labelledanti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebasedDTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50kDa. Radioimmunoconjugation with 177Lu was reacted for 15 min at room temperature. Theradiolabeling yield was >99%, and it was stable in human serum without any fragmentation ordegradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cellsurfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonalantibody for the targeting of colon cancer was effectively radioimmunoconjugated with 177Lu. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell bindingassay. In addition, the antibody’s tumor targeting ability was demonstrated with very high uptakein tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer withhighly expressed CD44.
Abstract
CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrixinteractions. In particular, splice variants of CD44 are particularly overexpressed in a large numberof malignancies and carcinomas. In this study, the 177Lu-labelled CD44 targeting antibodywas prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with theequivalent molar ratio of cysteine-based DTPA-NCS and radioimmunoconjugated with 177Lu atroom temperature within 15 minutes. The stability was tested in human serum. An in vitro studywas carried out in HT-29 human colon cancer cell lines. For the biodistribution study 177Lu-labelledanti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebasedDTPA-NCS and purified by a centricon filter system having a molecular cut-off of 50kDa. Radioimmunoconjugation with 177Lu was reacted for 15 min at room temperature. Theradiolabeling yield was >99%, and it was stable in human serum without any fragmentation ordegradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cellsurfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. The anti-CD44 monoclonalantibody for the targeting of colon cancer was effectively radioimmunoconjugated with 177Lu. The in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell bindingassay. In addition, the antibody’s tumor targeting ability was demonstrated with very high uptakein tumors. This radioimmunoconjugate is applicable to therapy in human colon cancer withhighly expressed CD44.
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