Radioactive ion beam range adaptation in mouse tumors using in-beam PET

Background Treatment adaptation is particularly critical in particle therapy, where even small range deviations can compromise target coverage or lead to unintended dose delivered to surrounding healthy tissues. In-beam positron emission tomography (PET) has emerged as a promising approach for range verification during irradiation with protons or stable carbon ion beams. However, its clinical use is limited by low signal-to-noise ratio and by the spatial mismatch between activity and dose distributions, reducing verification accuracy and limiting timely intervention. Methods We used radioactive ion beams for real-time range adaptation in 10 weeks old C3H/ HeNRj female mice bearing LM8-osteosarcoma tumors. Three 11 C beam range settings were planned: short (S), right (R), and long (L). The range of a collimated monoenergetic probing beam was monitored in real-time with the SIRMIO in-beam PET scanner by tracking the activity peak along the beam path, while range adaptation was achieved with a remotely controlled range shifter. Each plan (S, R and L) was also delivered, and tumor growth, toxicity assays, and histological analyses were performed to evaluate each treatment outcomes. Results Dynamic repositioning of the 11 C beam produced spatially resolved PET signals that correlated with distinct biological outcomes. Toxicity was observed only in the L group, while adequate tumor coverage was achieved in both R and L groups. In contrast, the S group showed continued tumor growth. Conclusions We provide the first demonstration that in-beam imaging of radioactive ion beams can enable real-time range-guided radiotherapy in a living organism. These findings establish radioactive ion beams as a promising platform for precision range-guided particle therapy.