Antibody-based cancer treatment with ultra-short range Auger electron-emitting radionuclides: dual receptor and DNA targeting strategies.

The long-heralded potential of targeted cancer treatment using monoclonal antibodies is finally being realized. Several antibodies are already used in the oncology clinic and many others are undergoing preclinical evaluation. In addition to the development of unconjugated antibodies, there is intense interest in the potential clinical use of antibodies as vehicles for targeting cytotoxic agents specifically to cancer cells. For example, radioimmunotherapy which involves the use of antibodies to deliver radionuclides to target cells is an approved treatment modality for cancer. Our laboratory is involved in developing technologies for radioimmunotherapy using a unique class of radionuclides, known as Auger electron emitters. A key feature of the Auger electrons emitted by these radionuclides is that they traverse very small ranges (molecular dimensions) in biological tissues. The emission of Auger electrons results in a gradient of energy deposition with the majority of the radiochemical damage occurring in the immediate vicinity (within a few cubic nanometers) of the decaying radionuclide. Therefore, realizing the full potential of Auger electron emitting isotopes in radioimmunotherapy requires more sophisticated approaches than directly radiolabeling anticancer antibodies. Strategies which involve targeting the radionuclide not only to cancer cells but also to the DNA of those cells are necessary. In this paper potential dual, receptor and DNA, targeting systems for radioimmunotherapy with Auger electron-emitting radionuclides are discussed.