DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair
Yousef Khazaei Monfared,
Pedram Heidari,
Samuel J. Klempner,
Umar Mahmood,
Aparna R. Parikh,
Theodore S. Hong,
Matthew R. Strickland,
Shadi A. Esfahani
Affiliations
Yousef Khazaei Monfared
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Pedram Heidari
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Samuel J. Klempner
Division of Hematology-Oncology, Department of Medicine, Mass General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Umar Mahmood
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Aparna R. Parikh
Division of Hematology-Oncology, Department of Medicine, Mass General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Theodore S. Hong
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Matthew R. Strickland
Division of Hematology-Oncology, Department of Medicine, Mass General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Shadi A. Esfahani
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated. This results in increased mutagenesis and genomic instability within the cancer cells, a known driver of cancer progression and therapeutic resistance. On the other hand, the inherent instability of the genome in rapidly dividing cancer cells can be exploited as a tool to kill by imposing DNA damage with radiopharmaceuticals. As the field of targeted radiopharmaceutical therapy (RPT) is rapidly growing in oncology, it is crucial to have a deep understanding of the impact of systemic radiation delivery by radiopharmaceuticals on the DNA of tumors and healthy tissues. The distribution and activation of DNA damage and repair pathways caused by RPT can be different based on the characteristics of the radioisotope and molecular target. Here we provide a comprehensive discussion of the biological effects of RPTs, with the main focus on the role of varying radioisotopes in inducing direct and indirect DNA damage and activating DNA repair pathways.
