PT  - JOURNAL ARTICLE
AU  - Zhongli Cai
AU  - Yongkyu Luke Kwon
AU  - Raymond M. Reilly
TI  - 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
AID  - 10.2967/jnumed.116.175695
DP  - 2017 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 339--345
VI  - 58
IP  - 2
4099  - http://jnm.snmjournals.org/content/58/2/339.short
4100  - http://jnm.snmjournals.org/content/58/2/339.full
SO  - J Nucl Med2017 Feb 01; 58
AB  - 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.