S2503
Radiobiology - Biology of novel irradiation techniques
ESTRO 2026
Results: Carbon-ion irradiation of the on-chip microvascular network resulted in dose-dependent microvascular damage (Figure 2).With increasing dose, the microvascular length density (i.e., the vessel length per unit area) decreased progressively. Over time, the effect of the dose became more pronounced (linear regression slopes: days 1–4, − 0.5 to − 2%/Gy, p > 0.1; day 7, − 2.3%/Gy, p < 0.05; day 9, − 2.8%/Gy, p < 0.01; day 10, − 3.4%/Gy, p < 0.01).Similarly, quantification of the area covered by the microvascular network demonstrated dose-dependent microvascular damage (linear regression slopes: days 1–4, − 0.27 to − 0.46 Gy- 1, p > 0.1; day 7, − 0.82 Gy-1, p < 0.05; day 9, − 0.89 Gy- 1, p < 0.05; day 10, − 1.2 Gy-1, p < 0.01).These results suggest microvascular damage and rarefaction after carbon-ion irradiation, consistent with previous reports of carbon-ion–induced capillary damage (6,7).
Digital Poster 751 Carbon ion irradiation induces microvascular regression in preclinical models on-chip Luca Possenti 1 , Sofia Tartaro 1 , Alexandra Charalampopoulou 2,3 , Alfredo Mirandola 2 , Valentina Doldi 4 , Angelica Facoetti 2 , Chiara Arrigoni 5,6 , Ester Orlandi 2,7 , Nadia Zaffaroni 4 , Marco Pullia 2 , Matteo Moretti 5,6 , Tiziana Rancati 1 1 Data Science Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2 CNAO, National Center for Oncological Hadrontherapy, Pavia, Italy. 3 IUSS, University School for Advanced Studies, Pavia, Italy. 4 Molecular Pharmacology Unit, Fondazione IRCCS
Istituto Nazionale dei Tumori, Milan, Italy. 5 Regenerative Medicine Division, Institute for
Translational research Università della Svizzera Italiana (USI) - Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland. 6 Euler Institute, Biomedical Sciences Faculty, Università della Svizzera Italiana (USI), Lugano, Switzerland. 7 Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy Purpose/Objective: Carbon ion irradiation induces clustered and complex DNA damage, resulting in greater biological efficiency than photons (1). In endothelial cells, these effects can trigger microvascular regression through endothelial apoptosis, barrier disruption, and suppression of angiogenic signaling (2). Understanding radiation- induced microvascular regression would help elucidate the vascular contribution to normal tissue injury and tumor response after carbon ion therapy. Material/Methods: We developed a microvasculature-on-chip model based on established designs (3). The microfluidic device enabled the vasculogenic formation of a 3D microvascular network from GFP-HUVECs and fibroblasts embedded in a fibrin–thrombin gel. A custom irradiation phantom was assembled from a solid water phantom, a Petri dish with a 3D-printed insert, and PMMA slabs to optimize thickness for Spread-Out Bragg Peak (SOBP) carbon ion irradiation (4, Figure 1). The microvascular networks were irradiated with up to 8 Gy and imaged by fluorescence microscopy up to 10 days. Culture media was replaced daily. Vascular networks were quantified using ImageJ (thresholding and tubeness filtering) and the MATLAB plugin μ VES (5).
Conclusion: Carbon ion irradiation induced measurable microvascular damage in a preclinical
microvasculature-on-chip model. These findings support the use of such platforms to investigate radiation-induced vascular damage and to advance understanding of microvascular responses relevant to hadron therapy.Acknowledgments The AIRC Investigator Grant no. IG21479 supported this work. References: 1- Durante et al. (2021). Nature Reviews Physics, 3(12), 777–7902- Garcia-Barros et al. (2003). Science, 300(5622), 1155–11593- Offeddu et al. (2019). Small, 15(46), 19023934- Possenti et al. (2025). Radiotherapy and Oncology, 206, S3944-S39455- Rota et al. (2025). Bioengineering & Translational Medicine, 8(5)6- Takahashi et al. (2003). Cancer Research, 63(14), 4253– 42577- Li et al. (2023). Radiation Research, 200(3). Keywords: microvasculature; carbon ion; on-chip
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