Monte Carlo N-Particle (MCNP) Modeling of the Cellular Dosimetry of<sup>64</sup>Cu: Comparison with MIRDcell S Values and Implications for Studies of Its Cytotoxic Effects
Bibliographic record
Abstract
<sup>64</sup>Cu emits positrons as well as β<sup>−</sup> particles and Auger and internal conversion electrons useful for radiotherapy. Our objective was to model the cellular dosimetry of <sup>64</sup>Cu under different geometries commonly used to study the cytotoxic effects of <sup>64</sup>Cu. <b>Methods:</b> Monte Carlo N-Particle (MCNP) was used to simulate the transport of all particles emitted by <sup>64</sup>Cu from the cell surface (CS), cytoplasm (Cy), or nucleus (N) of a single cell; monolayer in a well (radius = 0.32–1.74 cm); or a sphere (radius = 50–6,000 μm) of cells to calculate S values. The radius of the cell and N ranged from 5 to 12 μm and 2 to 11 μm, respectively. S values were obtained by MIRDcell for comparison. MCF7/HER2-18 cells were exposed in vitro to <sup>64</sup>Cu-labeled trastuzumab. The subcellular distribution of <sup>64</sup>Cu was measured by cell fractionation. The surviving fraction was determined in a clonogenic assay. <b>Results:</b> The relative differences of MCNP versus MIRDcell self-dose S values (S<sub>self</sub>) for <sup>64</sup>Cu ranged from −0.2% to 3.6% for N to N (S<sub>N←N</sub>), 2.3% to 8.6% for Cy to N (S<sub>N←Cy</sub>), and −12.0% to 7.3% for CS to N (S<sub>N←CS</sub>). The relative differences of MCNP versus MIRDcell cross-dose S values were 25.8%–30.6% for a monolayer and 30%–34% for a sphere, respectively. The ratios of S<sub>N←N</sub> versus S<sub>N←Cy</sub> and S<sub>N←Cy</sub> versus S<sub>N←CS</sub> decreased with increasing ratio of the N of the cell versus radius of the cell and the size of the monolayer or sphere. The surviving fraction of MCF7<b>/</b>HER2-18 cells treated with <sup>64</sup>Cu-labeled trastuzumab (0.016–0.368 MBq/μg, 67 nM) for 18 h versus the absorbed dose followed a linear survival curve with α = 0.51 ± 0.05 Gy<sup>−1</sup> and <i>R</i><sup>2</sup> = 0.8838. This is significantly different from the linear quadratic survival curve of MCF7<b>/</b>HER2-18 cells exposed to γ-rays. <b>Conclusion:</b> MCNP- and MIRDcell-calculated S values agreed well. <sup>64</sup>Cu in the N increases the dose to the N in isolated single cells but has less effect in a cell monolayer or small cluster of cells simulating a micrometastasis, and little effect in a sphere analogous to a tumor xenograft compared with <sup>64</sup>Cu in the Cy or on the CS. The dose deposited by <sup>64</sup>Cu is less effective for cell killing than γ-rays.
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How this classification was reachedexpand
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) | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".