A GATE simulation study for dosimetry in cancer cell and micrometastasis from the 225Ac decay chain
Why this work is in the frame
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Bibliographic record
Abstract
Abstract Background Radiopharmaceutical therapy (RPT) with alpha-emitting radionuclides has shown great promise in treating metastatic cancers. The successive emission of four alpha particles in the 225 Ac decay chain leads to highly targeted and effective cancer cell death. Quantifying cellular dosimetry for 225 Ac RPT is essential for predicting cell survival and therapeutic success. However, the leading assumption that all 225 Ac progeny remain localized at their target sites likely overestimates the absorbed dose to cancer cells. To address limitations in existing semi-analytic approaches, this work evaluates S -values for 225 Ac’s progeny radionuclides with GATE Monte Carlo simulations. Methods The cellular geometries considered were an individual cell (10 µm diameter with a nucleus of 8 µm diameter) and a cluster of cells (micrometastasis) with radionuclides localized in four subcellular regions: cell membrane, cytoplasm, nucleus, or whole cell. The absorbed dose to the cell nucleus was scored, and self- and cross-dose S -values were derived. We also evaluated the total absorbed dose with various degrees of radiopharmaceutical internalization and retention of the progeny radionuclides 221 Fr ( t 1/2 = 4.80 m) and 213 Bi ( t 1/2 = 45.6 m). Results For the cumulative 225 Ac decay chain, our self- and cross-dose nuclear S -values were both in good agreement with S -values published by MIRDcell, with per cent differences ranging from − 2.7 to − 8.7% for the various radionuclide source locations. Source location had greater effects on self-dose S -values than the intercellular cross-dose S -values. Cumulative 225 Ac decay chain self-dose S -values increased from 0.167 to 0.364 GyBq −1 s −1 with radionuclide internalization from the cell surface into the cell. When progeny migration from the target site was modelled, the cumulative self-dose S -values to the cell nucleus decreased by up to 71% and 21% for 221 Fr and 213 Bi retention, respectively. Conclusions Our GATE Monte Carlo simulations resulted in cellular S -values in agreement with existing MIRD S -values for the alpha-emitting radionuclides in the 225 Ac decay chain. To obtain accurate absorbed dose estimates in 225 Ac studies, accurate understanding of daughter migration is critical for optimized injected activities. Future work will investigate other novel preclinical alpha-emitting radionuclides to evaluate therapeutic potency and explore realistic cellular geometries corresponding to targeted cancer cell lines.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it