Radionuclide treatments of cancer: molecular mechanisms, biological responses, histopathological changes, and role of PET imaging

Abstract

Radiation treatments [radiotherapy and radionuclide treatments (RNTs)] are one of the main and effective treatment modalities of cancer. Globally, the number of cancer patients treated with radionuclides are much less as compared to number of radiotherapy cases but with the development of new radiotracers, most notably 177Lu and 225Ac-labeled prostate-specific membrane antigen ligands, and 223Ra-dichloride for prostate cancer and 177Lu-somatostatin analogs for neuroendocrine tumors, there is a significant rise in RNTs in the last decade. As therapeutic applications of nuclear medicine is on the rise, the aim of this review is to summarize biological responses to radiation treatments and molecular mechanisms of radiation-induced cell death (e.g. ionization, DNA damages such as double-strand breaks, DNA repair mechanisms, types of cell deaths such as apoptosis, necrosis, and immunogenic cell death), histopathological changes with radiation treatments, and role of PET imaging in RNTs as part of radionuclide theranostics for selecting and planning patients for RNTs, dosimetry, predicting and assessing response to RNTs, predicting toxicities, and other possible PET findings which may be seen after RNTs such as activation of immune system.