Lognormal Distribution of Cellular Uptake of Radioactivity: Monte Carlo Simulation of Irradiation and Cell Killing in 3-Dimensional Populations in Carbon Scaffolds

Rajon, Didier A.; Bolch, Wesley E.; Howell, Roger W.

doi:10.2967/jnumed.110.080044

Cited by 21 publications

(49 citation statements)

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“…The dependence of the survival curves on (1) the electron energy and (2) the distribution of radioactivity among the cells (i.e., uniform or lognormal distribution) was studied. 32 This earlier study showed that the surviving fraction depends strongly on both electron energy and activity distribution. Still, the study did not explore how the response depended on the percentage of cells that were labeled.…”

Section: Introductionmentioning

confidence: 99%

“…31 In order to better understand the contribution of a multitude of parameters on the dose response, our research groups recently developed a computer model that simulated the 3D tissue culture model. 32 The computer model combines a micro-computed tomography (μCT) image of a Cytomatrix TM carbon scaffold with a 6-μm voxel size and a cluster of 10 6 cell nuclei randomly positioned throughout the pores of the carbon matrix. Coupling a Monte Carlo transport code to the computer model allows one to record both the self-and the cross-dose for each cell.…”

Section: Introductionmentioning

confidence: 99%

“…The self-and cross-doses are then used to determine the surviving fraction of the 10 6 cell assembly. 32 Survival curves are constructed by gradually increasing the number of decays per simulation. In the previous work, monoenergetic electron sources were considered and it was assumed that all the cells were labeled (100% labeled).…”

Section: Introductionmentioning

confidence: 99%

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Survival of tumor and normal cells upon targeting with electron‐emitting radionuclides

2012

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Purpose: Previous studies have shown that the mean absorbed dose to a tissue element may not be a suitable quantity for correlating with the biological response of cells in that tissue element. Cell survival can depend strongly on the distribution of radioactivity at the cellular and multicellular levels. Furthermore, when cellular absorbed doses are examined, the cross-dose from neighbor cells can be less radiotoxic than the self-dose component. To better understand how the nonuniformity of activity among cells can affect the dose response, a computer model of a 3D tissue culture was previously constructed and showed that activity distribution among cells is significantly more relevant than the mean absorbed dose for low-energy-electron emitters. The present work greatly expands upon those findings. Methods: In the present study, we used this same computer model but restricted the number of labeled cells to a fraction of the whole cell population (50%, 10%, and 1%, respectively). The labeled cells were randomly distributed among the whole cell population. Results: While the activity distribution is an important factor in determining the tissue response for low-energy-electron emitters, the fraction of labeled cells has an even more pronounced effect on survival response. For all electron energies studied, reducing the percentage of cells labeled significantly increases the surviving fraction of the whole population. Conclusions: This study provides abundant information on killing tumor and normal cells under some conditions relevant to targeted radionuclide therapy of isolated tumor cells and micrometastases. The percentage of cells labeled, activity distribution among the labeled cells, and electron energy play key roles in determining their response. Most importantly, and not previously demonstrated, lognormal activity distributions can have a profound impact on the response of the tumor cells even when the radionuclide emits high-energy electrons.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Survival of tumor and normal cells upon targeting with electron‐emitting radionuclides

2012

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“…The study by Rajon et al (11) in this issue of The Journal of Nuclear Medicine presents a theoretic 3-dimensional tissue-culture model that more realistically recapitulates the variability of cell activity than previous models and, combined with dose-response models, provides new and important insights into the radiation dose distribution and biologic effect of heterogeneously deposited internal radionuclides.…”

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confidence: 99%

“…The individually optimized radionuclide or cocktail of radionuclides (25), tumor dose, and administered activity could then be prescribed for a patient's specific histologic tumor type (i.e., shape parameter value) using mean tumor doses per unit of administered activity derived on a case-by-case basis from routine quantitative imaging studies. With increasingly realistic dosimetric analyses-such as the method proposed by Rajon et al (11)-and the biologic insights they provide, such a hypothetical leap forward warrants at least some consideration.…”

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confidence: 99%

Cell-Level Dosimetry and Biologic Response Modeling of Heterogeneously Distributed Radionuclides: A Step Forward

Zanzonico

2011

J Nucl Med

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Targeted Radionuclide Therapy

Jurcic¹,

Wong²,

Knox³

et al. 2016

Clinical Radiation Oncology

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Lognormal Distribution of Cellular Uptake of Radioactivity: Monte Carlo Simulation of Irradiation and Cell Killing in 3-Dimensional Populations in Carbon Scaffolds

Cited by 21 publications

References 27 publications

Survival of tumor and normal cells upon targeting with electron‐emitting radionuclides

Survival of tumor and normal cells upon targeting with electron‐emitting radionuclides

Cell-Level Dosimetry and Biologic Response Modeling of Heterogeneously Distributed Radionuclides: A Step Forward

Targeted Radionuclide Therapy

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