Dra. Belén Cortés – Radiobiology and Biological Applications at CMAM-UAM

Proton therapy has gained increasing relevance due to its distinct physical advantage, the Bragg peak, which enables precise dose deposition within tumors while sparing surrounding healthy tissue. Despite its clinical adoption, key radiobiological mechanisms underlying proton response, including Linear Energy Transfer (LET)–dependent effects and the emerging FLASH (ultra-high dose rate) phenomenon, remain insufficiently understood. Addressing these knowledge gaps requires experimental platforms capable of delivering highly controlled and reproducible irradiation conditions that are difficult to achieve in clinical environments. In this context, dedicated accelerator-based infrastructures such as the CMAM 5 MV Tandem system play a crucial complementary role. CMAM uniquely provides monoenergetic proton beams in the mid-LET range (1–10 MeV) without energy degraders, narrow energy spreads, and conventional and FLASH dose rates, all essential features for systematic radiobiology investigations.

Recent upgrades at CMAM have focused on optimizing the proton irradiation beamline for both conventional and FLASH delivery. These developments include automated sample positioning, real-time monitoring through multichannel radiochromic film dosimetry to correct for LET-dependent quenching and expanded beamline control to ensure dose-rate stability across the full operational range. The platform is continuing to evolve to enhance scalability and versatility, enabling applications in radiobiology, materials research, and detector characterization.
Within this optimized experimental framework, in vitro studies using U-87MG glioblastoma cells were performed to investigate how variations in LET, cell density, and iron oxide nanoparticle (IONP)–mediated radiosensitization influence proton-induced biological responses. Irradiations at 10 MeV, with precise beam modulation to simulate different positions along the Bragg peak, revealed increased cell death and reduced clonogenic survival in higher-LET regions. IONP pre-treatment significantly intensified these effects, reducing cell viability and inducing pronounced cell-cycle arrest.