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Table 1. Literature article search approach. Database Keywords Results

Table 2. Rules for screening articles. Inclusion criteria

Exclusion criteria

� Participants were cancer patients undergoing � Gamma-H2AX did not identify individual radiosensitivity in radiopharmaceutical therapy cancer patients. � DDR was assessed by the increase in H2AX foci � The entire article could not be obtained in PDF format. � Gamma-H2AX predicts the individual radiosensitivity in cancer patients. � Articles were published during or before April 2024 � Articles were written in English

Purnami et al., 2023; Widjaja et al., 2022). Some individuals may have a higher sensitivity to radiation, meaning they may experience more severe side effects from radiopharmaceutical therapy compared to others. Factors contributing to individual radiosensitivity include genetic predisposition, age, overall health, and previous radiation exposure( Vinnikov and Belyakov, 2022).

Radiopharmaceutical therapy aims to deliver a therapeutic radiation dose to target cancer cells while minimizing damage to healthy tissues. However, individuals with higher radiosensitivity may experience increased side effects such as radiation dermatitis, nausea, fatigue, and bone marrow suppression( Fu et al., 2023; Khazaei Monfared et al., 2023). Healthcare providers take individual radiosensitivity into account when planning and administering radiopharmaceutical therapy. They may adjust the dosage or treatment schedule based on the patient’ s sensitivity and closely monitor for adverse reactions( Dewaraja et al., 2022).

Gamma-H2AX is a marker that detects DNA damage produced by ionizing radiation, such as that utilized in radiopharmaceutical therapy( Djuzenova et al., 2015, 2013). When cells are exposed to radiation, double-strand breaks develop in the DNA, causing the histone variant H2AX phosphorylation. These phosphorylated H2AX molecules generate foci around DNA damage sites, which can be visualized and quantified with immunofluorescence microscopy( Derlin et al., 2021; Djuzenova et al., 2013; Srivastava et al., 2009)

The level of gamma-H2AX foci formation can measure the extent of DNA damage induced by radiation exposure. It is often used in research to study individual radiosensitivity, as differences in the response of cells to radiation can be observed among individuals. Some people may have a higher baseline level of gamma-H2AX foci formation, indicating increased DNA damage sensitivity( Kawashima et al., 2020).

Understanding individual radiosensitivity through markers like gamma-H2AX can be valuable for personalized treatment planning in radiopharmaceutical therapy. By assessing a patient’ s baseline level of DNA damage sensitivity, healthcare providers can tailor the dosage and treatment regimen to minimize adverse effects while maximizing therapeutic efficacy( Djuzenova et al., 2015; Srivastava et al., 2009).

Additionally, research into individual radiosensitivity and gamma-H2AX may help identify biomarkers that predict patient response to radiopharmaceutical therapy, allowing for more precise patient selection and treatment optimization. Gamma-H2AX and individual radiosensitivity are essential in developing and administering radiopharmaceutical therapy, contributing to personalized treatment strategies and improved patient outcomes( Cai et al., 2008; Kawashima et al., 2020).

A systematic review on gamma-H2AX, individual radiosensitivity, and radiopharmaceutical therapy would aim to evaluate the current body of research on these topics comprehensively. By systematically synthesizing existing evidence, such a review can contribute to understanding the role of gamma-H2AX and individual radiosensitivity in guiding and optimizing radiopharmaceutical therapy for cancer patients.

2 Literature review

2.1 Literature search strategy

A comprehensive data search was undertaken using three electronic databases: PubMed Central( PMC), ScienceDirect, and Scopus. The literature analysis included phrases such as“ individual radiosensitivity,”“ gamma-H2AX,”“ radiopharmaceuticals,” and“ cancer patients,” as shown in Table 1. Suitable publications were discovered by reviewing the references and included if they matched the inclusion criteria( Tab. 2). The