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

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.

We used radioactive ion beams for real-time range adaptation in 10 weeks old C3H/ HeNRj female mice bearing LM8-osteosarcoma tumors. Three ¹¹C 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.

Dynamic repositioning of the ¹¹C 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.

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.