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
64Cu emits positrons as well as β− particles and Auger and internal conversion electrons useful for radiotherapy. Our objective was to model the cellular dosimetry of 64Cu under different geometries commonly used to study the cytotoxic effects of 64Cu. Methods: Monte Carlo N-Particle (MCNP) was used to simulate the transport of all particles emitted by 64Cu 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 64Cu-labeled trastuzumab. The subcellular distribution of 64Cu was measured by cell fractionation. The surviving fraction was determined in a clonogenic assay. Results: The relative differences of MCNP versus MIRDcell self-dose S values (Sself) for 64Cu ranged from −0.2% to 3.6% for N to N (SN←N), 2.3% to 8.6% for Cy to N (SN←Cy), and −12.0% to 7.3% for CS to N (SN←CS). 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 SN←N versus SN←Cy and SN←Cy versus SN←CS 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/HER2-18 cells treated with 64Cu-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−1 and R2 = 0.8838. This is significantly different from the linear quadratic survival curve of MCF7/HER2-18 cells exposed to γ-rays. Conclusion: MCNP- and MIRDcell-calculated S values agreed well. 64Cu 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 64Cu in the Cy or on the CS. The dose deposited by 64Cu is less effective for cell killing than γ-rays.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".