The review presented here lays out the present state of the art in the field of radionuclide therapies specifically targeted against the nucleus of cancer cells, focussing on the use of Auger-electron-emitters. Nuclear localisation of radionuclides increases DNA damage and cell kill, and, in the case of Auger-electron therapy, is deemed necessary for therapeutic effect. Several strategies will be discussed to direct radionuclides to the nucleoplasm, even to specific protein targets within the nucleus. An overview is given of the applications of Auger-electron-emitting radionuclide therapy targeting the nucleus. Finally, a few suggestions are made as how radioimmunotherapy with nuclear targets can be improved, and the challenges that might be met, such as how to perform accurate dosimetry measurements, are examined.
Keywords: Auger-electron, radionuclide, radioimmunotherapy, nucleus, targeted radiotherapy, molecular radiotherapy, PRRT, Auger-Electron Radionuclide Therapy, cancer cells, Auger-electron-emitters, DNA damage, nucleoplasm, dosimetry, systemic chemotherapy, X-ray radiotherapy, mitotic catastrophe, tumour regression, metastatic lesions, thyroid ablation therapy, bone metastases, metaiodobenzylguanidine, metaastatobenzylguanidine, 32P-orthophosphate, 153Smethylenediamine tetra(methylene phosphonic acid), 111In-octreotide, 177Lu-octreotide, 211At-anti-Her2 affibodies, targeted or molecular radiotherapy, peptide receptor radionuclide therapy, 4He2+ particles, beta-particles, super-Coster-Kroning electrons, Coster-Kroning, reactive oxygen species, electron emission spectra, gamma-photon emissions, 125I-labelled 5-iododeoxyuridine, somatostatin, nuclear localisation sequence, peptide nucleic acids, lysosomal degradation, SKOV cells, radiation-induced bystander effect, tumour necrosis factor, 123/131I metaiodo-benzyl-guanidine, Exendin, DNA-binding ligand, methotrexate, paclitaxel, doxorubicin
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