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Background: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a promising new radiation therapy modality for treating bulky tumors. 224 Ra-carrying sources are inserted intratumorally, producing a therapeutic alpha-dose region with a total size of a few millimeter via the diffusive motion of 224 Ra's alpha-emitting daughters. Clinical studies of Alpha DaRT have reported 100% positive response (30%-100% shrinkage within several weeks), with post-insertion swelling in close to half of the cases. While dosimetry recommendations informed by the effects of edema are standard in some radiation therapy modalities, the effect of edema and tumor shrinkage on the absorbed dose delivered by Alpha DaRT is still unknown., Purpose: The aim of this work is to develop a simple model for Alpha-DaRT dose deposition in a time-dependent tissue volume in order to study the effect of geometrical changes in source location due to edema and tumor shrinkage on the delivered alpha particle dose., Methods: We perform FEM-based dose deposition modeling for a single Alpha-DaRT source inside shrinking and swelling tissues. Gradual volume change models were used for shrinkage and swelling, and an additional immediate volume gain model was also used for "worst case" swelling. Volume change rates were estimated from source location data from serial scans acquired at time of insertion and removal for seven patients treated using Alpha DaRT. We calculate absorbed dose profiles under both the high- and low-diffusion regimes described by the Diffusion-Leakage model., Results: Changes in tissue volume can lead to over- or underestimation of the calculated absorbed dose. In the low-diffusion regime, gradual tissue shrinkage can result in an increase of 100% and gradual swelling can result in a 35% decrease in absorbed dose compared to a calculation in static tissue. Although immediate post-insertion swelling can reduce the absorbed dose by close to 65% for very closely spaced sources, in all cases analyzed the final absorbed dose continues to exceed the 10 Gy target. These effects are less severe in the high-diffusion regime., Conclusions: These results indicate that tissue swelling and shrinkage can have a non-negligible effect on the tumor absorbed dose. Further study of tissue dynamics during Alpha-DaRT treatment will be necessary for improvements in dosimetry practice., (© 2025 American Association of Physicists in Medicine.)

Purpose: Diffusing alpha-emitters Radiation Therapy ("Alpha DaRT") is a new cancer treatment modality that employs radium-224-loaded metal sources implanted in solid tumors to disperse alpha-emitting atoms within a therapeutic "kill-zone" of a few millimeters around each source. Preclinical studies have demonstrated tumor growth delay in various cancer types, including glioblastoma multiforme, and the method is used in clinical trials for patients with skin and head and neck cancer. This study aims to assess the safety and feasibility of implementing Alpha DaRT for brain tumor treatment in a large animal model., Methods: Alpha-DaRT sources were delivered via image-guided stereotactic implantation into both hemispheres of eight swine. 1-3 layers of radial deployment of 7 sources were delivered through a single penetration point into each hemisphere. A 90-day follow-up period included clinical evaluation, brain MRI, head CT, blood, CSF, urine, and feces sampling, and an analysis of source location over time. Brain tissue pathology was performed on termination., Results: Alpha-DaRT sources were reproducibly and efficiently delivered to the brain cortex and subcortex. No unexpected abnormalities were detected in blood or CSF samples. MRI and CT scans revealed no evidence of major bleeding or infection. Measurements of 212 Pb in blood and CSF exhibited the expected exponential decay from day 7 to day 14 post-source implantation. Minimal spatial and temporal movements of the sources were noted. Histopathological analysis demonstrated locally confined findings in brain parenchyma in a very close proximity to the sources., Conclusion: Alpha-DaRT sources can be safely delivered into a large animal brain using image-guided stereotactic implantation. These findings support further exploration of Alpha DaRT as a potential treatment modality for brain tumors., Competing Interests: Declarations. Competing interests: YS serves as a paid medical advisor for Alpha Tau Medical Ltd. and receives equity. AP serves as a medical advisor for Alpha Tau Medical Ltd. and receives equity. RBD serves as CMO of Alpha Tau Medical Ltd. and receives compensation and equity. LA receives equity and has a research budget funded by the company. All other authors declare no conflict of interest., (© 2024. The Author(s).)