Biomedical Engineering Reference
In-Depth Information
Fig. 28.1
A schematic overview of the trafficking and nuclear localization of Auger-electron-
emitting radiopharmaceuticals (AER). AER can damage and kill cells by inducing membrane
damage, or by internalizing into the cell. Internalization can occur via receptor- or cell-penetrating-
peptide- mediated endocytosis, or happen via diffusion or transfection. Once in the cell, AER
internalized by endocytosis escape from the endosome, or are degraded by lysosomes. Nuclear
localization takes place via receptor-mediated nuclear transport, or via the nuclear pore complex,
which can happen via diffusion for smaller molecules, or via nuclear localization sequence (NLS)-
mediated active transport. AER can bind covalently to DNA, intercalate in the DNA helix, interact
with chromatin via receptors and scaffolding proteins, or cause ROS species. All of the above
results in DNA damage, which is either repaired, or leads to cytotoxicity. Even in cells which
have not been affected directly by AER, the radiation-induced bystander effect (RIBE) can induce
cytotoxicity via excreted signaling factors [
139
]
have shown promise in laboratory models have been exploited for Auger electron
radiotherapy. We restrict the discussion to those agents that have been tested in
clinical trials.
28.3.1
Radioimmunotherapy
One of the first agents to be evaluated against tumor antigens was monoclonal
antibodies. Auger electron emitters can be used to label mAbs that target either
the cell surface or the cytoplasm through a receptor-mediated internalizing process.
