Periodic Reporting for period 3 - BARB (Biomedical Applications of Radioactive ion Beams)
Reporting period: 2023-10-01 to 2025-03-31
Cancer remains one of the main causes of death worldwide. In 2022, >50% cancer patients in Europe underwent radiotherapy. While over 80% were treated using high-energy X-rays, the number of patients receiving accelerated protons or heavy ions (charged particle therapy: CPT) is rapidly growing, with over 300,000 patients treated up till now. Although CPT offers a better depth-dose distribution compared to common X-ray based techniques, range uncertainty and poor image guidance still limit its application. Improving accuracy is key to broadening the applicability of CPT. In BARB, we will open a new paradigm in the clinical use of CPT by using high-intensity radioactive ion beams (RIB), produced at GSI/FAIR-phase-0 in Darmstadt, for simultaneous treatment and visualization. This will reduce range uncertainty and extend the applicability of CPT to treatment of small lesions (e.g. metastasis and heart ventricles) with unprecedented precision. The Facility for Antiprotons and Ion Research (FAIR) is currently under construction at GSI. RIB are one of the main tools for basic nuclear physics studies in the new facility. As part of the ongoing FAIR-phase-0, an intensity upgrade will increase the light ion currents in the existing SIS18 synchrotron. Within this project BARB, we will study four beta+ emitters (10,11C, and 14,15O) and build an innovative hybrid detector for online positron emission tomography (PET) and gamma-ray imaging. This novel detector will acquire both prompt gamma-rays during the beam-on phase of the pulsed synchrotron beam delivery, and the delayed emission from beta+ annihilation during the pulse intervals. The technique will be further validated in vivo by applying it to treatment of small tumors in a mouse model. BARB will exploit the potential of the Bragg peak in medicine. The project will tweak RIB production in nuclear physics and validate the therapeutic potential of RIB therapy in vivo by empowering simultaneous treatment and visualization.
The project started in 2020 and was disturbed by two problems: the COVID-19 pandemics, and the Ukraine war. Both problems had an impact on the availability of beamtime at GSI, so that as yet it was only possible to have beamtime in 2021, both with carbon and oxygen beams. The next beamtime windows, where we expect to gather the decisive results, are scheduled for February 2024 and February 2025. The main activities can be divided into 4 parts:
(a)Modelling for BARB. We have performed an assessement in silico of the potential advantages of RIB in therapy working on treatment plans in real patients. Our results (see publication Sokol et al., Sci. Rep. 2022) shows significant reduction in toxicity for both serial (e.g. optical nerves) and parallel (e.g. liver) organs
(b)The first experiment with C-ions at the fragment separator (FRS) vault S4 allowed a full characterization of the radioactive carbon beams (see Boscolo et al., NIM 2022) and the first PET images of these beams (see Kostyleva et al., PMB 2023) that clearly showed how the resolution of te range measurement is improved when RIB are used.
(c)For biology experiments, we need to transport the radioactive beam from FRS to the medical vault (Cave M) at GSI. The beamline has now been commissioned (manuscript in preparation).
(d)Thanks to the new transfer line we could make experiments with 15O beams in Cave M (manuscript in preparation).
(a)Modelling for BARB. We have performed an assessement in silico of the potential advantages of RIB in therapy working on treatment plans in real patients. Our results (see publication Sokol et al., Sci. Rep. 2022) shows significant reduction in toxicity for both serial (e.g. optical nerves) and parallel (e.g. liver) organs
(b)The first experiment with C-ions at the fragment separator (FRS) vault S4 allowed a full characterization of the radioactive carbon beams (see Boscolo et al., NIM 2022) and the first PET images of these beams (see Kostyleva et al., PMB 2023) that clearly showed how the resolution of te range measurement is improved when RIB are used.
(c)For biology experiments, we need to transport the radioactive beam from FRS to the medical vault (Cave M) at GSI. The beamline has now been commissioned (manuscript in preparation).
(d)Thanks to the new transfer line we could make experiments with 15O beams in Cave M (manuscript in preparation).
BARB aims at exploring the application of radioactive beams (RIBs) for simultaneous treatment and imaging during radiotherapy, which promises to improve the accuracy of the in vivo ion range verification and subsequently allow for a more accurate treatment of tumors close to critical structures. In this project, the research group at the Chair of Experimental Physics – Medical Physics of LMU Munich is responsible for developing a dedicated in-beam hybrid detection scheme exploiting all secondary photon emissions induced during the beam delivery, while the GSI biophysics department is in charge of the dosimetric and physical characterization of the RIBs (together with the FRS group) as well as the in vivo experiment demonstrating the feasibility of a small animal tumor irradiation with RIBs.
This proposal has three main objectives:
(1) To test the new spherical in-beam PET scanner detector for visualizing the RIBs in different phantoms as well as in the mouse.
(2) To apply the RIBs for the first time for simultaneous tumor treatment and beam range verification in a mouse; we expect to achieve the same tumor control rate as with stable beams, while reducing the normal tissue toxicity.
(3) To visualize the potential vascular damage (of the potential mechanisms underlying the effectiveness of single-fraction high-dose radiotherapy) by monitoring the biological washout of the RIBs PET signal.
This proposal has three main objectives:
(1) To test the new spherical in-beam PET scanner detector for visualizing the RIBs in different phantoms as well as in the mouse.
(2) To apply the RIBs for the first time for simultaneous tumor treatment and beam range verification in a mouse; we expect to achieve the same tumor control rate as with stable beams, while reducing the normal tissue toxicity.
(3) To visualize the potential vascular damage (of the potential mechanisms underlying the effectiveness of single-fraction high-dose radiotherapy) by monitoring the biological washout of the RIBs PET signal.