Radioprotection 2025, 60( 3), 285 – 292 © T. Kisnanto et al., Published by EDP Sciences 2025 https:// doi. org / 10.1051 / radiopro / 2025004
Available online at: www. radioprotection. org
ARTICLE Gamma-H2AX as a biomarker to assess individual radiosensitivity for radiopharmaceutical therapy in cancer patients: a systematic review T. Kisnanto 1, 2, D. Ramadhani 2, E. H Purwaningsih 3, R. W Hakim 3, I. K. H Basri 2, T. S Humani 2, H. N. E Surniyantoro 2, M. Syaifudin 2, S. Purnami 4 and D. A Suryandari 5,*
1 Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia. 2 Research Center for Radioisotope, Radiopharmaceutical, and Biodosimetry Technology, Research Organization for Nuclear Energy
National Research and Innovation Agency, Tangerang, Indonesia. 3 Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia. 4 Research Center for Safety, Metrology, and Nuclear Quality Technology, Research Organization for Nuclear Energy National Research
and Innovation Agency, Tangerang, Indonesia. 5 Department of Medical Biology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
Received: 19 July 2024 / Accepted: 31 January 2025
Abstract – Radiopharmaceutical therapy offers targeted and potent cancer treatment, but individual responses vary, necessitating personalized approaches for optimal outcomes. Gamma-H2AX, a phosphorylated form of histone, has become a sensitive indicator of DNA double-strand breaks caused by ionizing radiation. Gamma-H2AX assays in radiopharmaceutical therapy offer a non-invasive way to assess individual radiosensitivity, improving treatment optimization and patient classification. This systematic review examines the use of gamma-H2AX as a biomarker for determining individual radiosensitivity in cancer patients receiving radiopharmaceutical therapy. An in-depth search for supporting publications utilized three popular electronic databases: PubMed Central( PMC), ScienceDirect, and Scopus. Specific keywords determine article limits. Every existing article was examined and appraised independently using the PICO method( participants, intervention / exposure, comparison, and outcome). Eighty-one articles were identified, 49 were screened based on title and abstract, and 32 were excluded. Six articles were worthy, but only two were considered in this research. Based on these two articles, it is possible to conclude that the gamma-H2AX foci marker in peripheral blood cells of patients receiving radiopharmaceutical therapy was promising for predicting treatment response and individual radiosensitivity. However, this research must be validated with more patients for a higher prospective value in future investigations.
Keywords: DNA damage response / gamma-H2AX / radiosensitivity / cancer / radiopharmaceutical therapy
1 Introduction
Radiopharmaceutical therapy technology uses radioactive substances to treat a variety of medical conditions, particularly cancer. The radioactive substance is given orally or intravenously, allowing it to specifically target cancer cells or diseased tissue while minimizing damage to surrounding healthy tissue( Derlin et al., 2021; Sgouros et al., 2020). Radiation emitted from radioactive substances can kill cancer cells or inhibit their growth. These compounds are designed to be absorbed and targeted at specific types of cancer cells( Cai et al., 2008; Vinnikov and Belyakov, 2022).
* Corresponding author: anitabio @ yahoo. co. uk
Radiopharmaceuticals commonly used in therapy include iodine-131 for thyroid cancer, strontium-89 and samarium-153 for bone metastases, and lutetium-177 and yttrium-90 for prostate cancer and neuroendocrine tumors( Dewaraja et al., 2022; Vinnikov and Belyakov, 2022). Nuclear medicine specialists often deliver radiopharmaceutical therapy, which requires close monitoring to ensure safety and efficacy. It can be used as the primary treatment or in combination with other therapies such as surgery, chemotherapy, or external beam radiation therapy( Gong and Miller, 2019; Raavi et al., 2021).
Individual radiosensitivity refers to the variation in how different individuals respond to radiation exposure. This sensitivity can influence radiopharmaceutical therapy’ s effectiveness and potential side effects( Chen et al., 2024;
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