Macrocyclic bifuncitonal ligandscontaining metal binding moieties and a functional unit for conjugation to abiomolecule have been employed for biomedical and radiopharmaceuticalapplications including radioimmunotherapy (RIT). A bifunctional ligand that cantightly and/or rapidly bind a therapeutic or diagnostic metal while beingconjugated to a highly sensitive antibody without compromising its biologicalactivity is a critical component for successful targeted therapy of cancer. Inthis presentation, synthesis of novel macrocyclic bifunctional ligandsfor RIT of cancer will be described. The key reaction step for the synthesis of thebifunctional ligands involves nucleophilic ring opening of aziridine oraziridinium ion by TACN or CYCLEN. The ligands in the isothiocyanate form wereconjugated to Herceptin, an antibody that selectively target the HER2 proteinwhich is overexpressed in various cancers including metastatic breast cancer. Thecorresponding ligand-Herceptin conjugate were evaluated for complexationkinetics and in vitro stability withthe metals for RIT.

Synthesis and biological evaluation of macrocyclic bifunctional ligands for cancer therapy

240th National Meeting (2010)

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