S2562
Radiobiology – Normal tissue radiobiology
ESTRO 2026
Hungary. 3 Department of Biochemistry and Molecular Biology, University of Science of Szeged, Faculty of Natural Sciences and Informatics, Szeged, Hungary Purpose/Objective: Nanoparticles (NPs) are widely explored in medicine for drug delivery, imaging, and enhancing radiation therapy. In radiation oncology, metallic NPs can increase tumor radiosensitivity in addition to the non- toxic effect on normal cells. Although their effects on cancer cells are well documented, their influence on normal tissues is less understood. This study employed a two-part experimental design to define the intrinsic radiosensitivity of 48 hours post- fertilization (hpf) zebrafish embryos (ZFe) and to evaluate the radiosensitizing efficacy of selected metallic and metal oxide nanoparticles (NPs) in developing healthy tissues. Material/Methods: To determine the dose-response relationship, 48 hpf embryos were subjected to a single dose of 250 keV photon radiation across an escalating dose range: 5, 10, 20, 25, 30, 35, and 40 Gy. This step serves to define the intrinsic radiation tolerance and the LD50/7d (Lethal Dose 50% at 7 days) for the specified developmental stage. To evaluate the nanoparticle- mediated radiosensitization, ZFe-s at 24 hpf were incubated for 24 hours (reaching 48 hpf at irradiation) with various sizes and concentrations of gold (AuNPs: 12, 47 nm; 5–50 mg/L), platinum (PtNPs: 5, 20 nm; 25– 75 mg/L), and hafnium oxide nanoparticles (HfO2NPs: 55–75 nm; 10, 30 µg/mL). Following the 24-hour exposure, embryos were thoroughly washed to remove non-internalized NPs and were subsequently arrayed into 96-well plates. NP-loaded embryos were exposed to a single, fixed, intermediate dose of 20 Gy photon radiation. Embryos were monitored for 7 days to assess survival, hatching, malformations (e.g. growth delay, pericardial edema), and photomotor response. Results: The dose-response study revealed a progressive decrease in survival and increased frequency of morphological abnormalities with doses above 20 Gy. AuNPs caused minimal toxicity, but 47 nm particles enhanced radiation-induced abnormalities from day 3 of observation. PtNPs were toxic at all sizes and concentrations, significantly reducing survival and hatching rates while increasing malformations. HfO2NPs showed no significant toxicity or morphological effects. Conclusion: The ZFe model proved suitable for nanoparticle toxicity screening. Although AuNPs and PtNPs enhanced radiation effects in the zebrafish embryo model, this likely reflects increased toxicity to normal tissues rather than therapeutic radiosensitization. In
contrast, HfO2NPs demonstrated lower toxicity, suggesting they may offer a safer profile and merit further investigation for potential use in radiotherapy.Acknowledgement: The ELI ALPS project (GINOP-2.3.6-15-2015-00001) is supported by the European Union and co-financed by the European Regional Development Fund. Keywords: nanoparticles,zebrafish,radiosensitization Poster Discussion 1685 Ketogenic diet ameliorates radiation proctitis through HMGCS2-dependent mechanism Lekun Fang, Dan Zhong, Shaomin Zou, Jieping Zhang, Manqi Meng Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Purpose/Objective: Radiation proctitis (RP) is a prevalent complication of radiotherapy for pelvic malignancies, characterized by sustained inflammation of colorectal tissue and an unmet need for effective therapies1. Although dietary interventions have been widely explored in intestinal disorders, their role in radiation-induced rectal injury remains unclear2,3. In this study, we aim to evaluate the effects of different dietary regimens on the pathogenesis of radiation proctitis and to elucidate the potential role of Hmgcs2, a key enzyme in ketogenesis, in mediating the effects of a ketogenic diet. Material/Methods: A mouse model of RP was established by delivering 25 Gy irradiation to the pelvic region while shielding the rest of the body4. Eight weeks post-irradiation, mice were euthanized for tissue collection. To assess dietary effects, mice with RP were divided into three groups receiving either normal diet, a high-fat diet, or a ketogenic diet. Colonoscopic and histopathological analyses were performed to evaluate disease severity. ZO-1,Occludin and MUC2 weredetected by Immunofluorescence analysis. Colorectal tissues were processed for RNA sequencing and histology. Results: Mice were fed a normal diet, high-fat diet, or ketogenic diet (a very high-fat, low-carbohydrate regimen) prior to radiation proctitis induction (Fig. 1a). The ketogenic diet group showed attenuated pathology with minimal erosive lesions, preserved mucosal architecture, and reduced submucosal thickness, whereas the high-fat diet group developed extensive erosive lesions and mucosal thickening (Fig. 1b-c).The transcriptomic analysis between control and RP mice tissues shows Hmgcs2 decreased in RP mice group, which is the key enzyme in ketogenesis. To further explore its functional role, Hmgcs2 - deficient mice were utilized
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