España Palomares, SamuelEspinosa Rodríguez, AndreaGarcia Diez, MiguelMartinez Nouvilas, VictorSánchez Tembleque Verbo, VíctorUdías Moinelo, José ManuelValladolid Onecha, VíctorFraile Prieto, Luis Mario2024-03-142024-03-142023-09-29Ibáñez-Moragues, M., Fernández-Barahona, I., Santacruz, R., Oteo, M., Luján-Rodríguez, V. M., Muñoz-Hernando, M., ... & Morcillo, M. Á. (2023). Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy. Molecules, 28(19), 6874.10.3390/molecules28196874https://hdl.handle.net/20.500.14352/102235Artículo firmado por 23 autoresProton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1–10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1420-3049https://www.mdpi.com/1420-3049/28/19/6874open access539.1RadiotherapyNanoparticleProton range verificationProton therapyIron oxide nanoparticlesZincIrradiationPrompt gamma radiationFísica nuclear2207 Física Atómica y Nuclear