Fig. 6

Examples of targeting vehicles for delivery of Auger electron (AE)-emitting radionuclides to cancer cells. Non-internalising monoclonal antibodies (mAbs) or peptides bind to cell-surface receptors and may kill cells through damaging the cell membrane. Internalising mAbs or peptides may be transported to the cell nucleus by appending nuclear localisation sequence (NLS) peptides or by an endogenous NLS present in some cell-surface receptors (e.g. EGFR or HER2) or combine internalising, endosomal escape and nuclear localizing sequences (modular nanotransporters). Nuclear localisation causes lethal DNA double-strand breaks (DSBs). Micelles or gold nanoparticles may be modified with mAbs or peptides to target cell surface receptors or are internalised non-specifically into cancer cells by endocytosis. ¹²⁵I-labelled anthracyclines diffuse into cancer cells and intercalate into DNA, while ¹²⁵I-2-iododeoxyuridine (¹²⁵I-IUdR) is taken up by nucleoside transporters and incorporated into DNA. These agents cause lethal DNA DSBs