Cellular dosimetry of (111)In using monte carlo N-particle computer code: comparison with analytic methods and correlation with in vitro cytotoxicity.
Our objective was to compare Monte Carlo N-particle (MCNP) self- and cross-doses from (111)In to the nucleus of breast cancer cells with doses calculated by reported analytic methods (Goddu et al. and Farragi et al.). A further objective was to determine whether the MCNP-predicted surviving fraction (SF) of breast cancer cells exposed in vitro to (111)In-labeled diethylenetriaminepentaacetic acid human epidermal growth factor ((111)In-DTPA-hEGF) could accurately predict the experimentally determined values.


METHODS
MCNP was used to simulate the transport of electrons emitted by (111)In from the cell surface, cytoplasm, or nucleus. The doses to the nucleus per decay (S values) were calculated for single cells, closely packed monolayer cells, or cell clusters. The cell and nucleus dimensions of 6 breast cancer cell lines were measured, and cell line-specific S values were calculated.


RESULTS
For self-doses, MCNP S values of nucleus to nucleus agreed very well with those of Goddu et al. (ratio of S values using analytic methods vs. MCNP = 0.962-0.995) and Faraggi et al. (ratio = 1.011-1.024). MCNP S values of cytoplasm and cell surface to nucleus compared fairly well with the reported values (ratio = 0.662-1.534 for Goddu et al.; 0.944-1.129 for Faraggi et al.). For cross doses, the S values to the nucleus were independent of (111)In subcellular distribution but increased with cluster size. S values for monolayer cells were significantly different from those of single cells and cell clusters. The MCNP-predicted SF for monolayer MDA-MB-468, MDA-MB-231, and MCF-7 cells agreed with the experimental data (relative error of 3.1%, -1.0%, and 1.7%). The single-cell and cell cluster models were less accurate in predicting the SF. For MDA-MB-468 cells, relative error was 8.1% using the single-cell model and -54% to -67% using the cell cluster model. Individual cell-line dimensions had large effects on S values and were needed to estimate doses and SF accurately.


CONCLUSIONS
MCNP simulation compared well with the reported analytic methods in the calculation of subcellular S values for single cells and cell clusters. Application of a monolayer model was most accurate in predicting the SF of breast cancer cells exposed in vitro to (111)In-DTPA-hEGF.
Department of Pharmaceutical Sciences, University of Toronto, Ontario, Canada.
Zhongli
Z
Cai
Jean-Philippe
JP
Pignol
Conrad
C
Chan
Raymond M
RM
Reilly
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003593:Cytoplasm / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008954:Models, Biological; D057054:Molecular Imaging; D009010:Monte Carlo Method; D004369:Pentetic Acid / Q000737:chemistry; D011381:Programming Languages; D011874:Radiometry / Q000379:methods*
D007205:Indium Radioisotopes; D004815:Epidermal Growth Factor; D004369:Pentetic Acid