Low-energy Electron Emitters for Targeted Radiotherapy of Small Tumours

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Abstract
The possibility of using electron emitters to cure a cancer with metastatic spread depends on the energy of the emitted electrons. Electrons with high energy will give a high, absorbed dose to large tumours, but the absorbed dose to small tumours or single tumour cells will be low, because the range of the electrons is too long. The fraction of energy absorbed within the tumour decreases with increasing electron energy and decreasing tumour size. For tumours smaller than 1 g, the tumour-to-normal-tissue mean absorbed dose-rate ratio, TND, will be low, e.g. for 131I and 90Y, because of the high energy of the emitted electrons. For radiotherapy of small tumours, radionuclides emitting charged particles with short ranges (a few microm) are required. A mathematical model was constructed to evaluate the relation between TND and electron energy, photon-to-electron energy ratio, p/e, and tumour size. Criteria for the selection of suitable radionuclides for the treatment of small tumours were defined based on the results of the TND model. In addition, the possibility of producing such radionuclides and their physical and chemical properties were evaluated. Based on the mathematical model, the energy of the emitted electrons should be < or = 40 keV for small tumours (< 1000 cells), and the photon-to-electron energy ratio, p/e, should be < or = 2 to achieve a high TND. Using the selection criteria defined, five low-energy electron emitters were found to be suitable: 58Co, 103mRh, 119Sb, 161Ho, and 189mOs. All of these nuclides decay by internal transition or electron capture, which yields conversion and Auger electrons, and it should be possible to produce most of them in therapeutic amounts. The five low-energy electron-emitting radionuclides identified may be relevant in the radiation treatment of small tumours, especially if bound to internalizing radiopharmaceuticals.