Cellular dosimetry of different radionuclides for targeted radionuclide therapy: Monte Carlo simulation

Sadremomtaz, Alireza; Masoumi, Mahboubeh

doi:10.1088/2057-1976/aade5d

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…For this purpose, we compared S values obtained for the same cellular shape in MCNP6.1 and Geant4-10.03 for concentric spheres (including MIRDcell) and truncated cones. The relative deviation between the codes was small (< 5%) and could be attributed to several factors: (1) the inclusion of δ-rays and energy-loss straggling in Monte Carlo calculations ignored by MIRDcell [10], (2) the use of a different cellular composition rather than water [28], (3) the use of different cross-sections and (4) β-spectra.…”

Section: Discussionmentioning

confidence: 99%

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

et al. 2020

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Background: Survival and linear-quadratic model fitting parameters implemented in treatment planning for targeted radionuclide therapy depend on accurate cellular dosimetry. Therefore, we have built a refined cellular dosimetry model for [ 177 Lu]Lu-DOTA-[Tyr 3 ]octreotate (177 Lu-DOTATATE) in vitro experiments, accounting for specific cell morphologies and sub-cellular radioactivity distributions. Methods: Time activity curves were measured and modeled for medium, membrane-bound, and internalized activity fractions over 6 days. Clonogenic survival assays were performed at various added activities (0.1-2.5 MBq/ml). 3D microscopy images (stained for cytoplasm, nucleus, and Golgi) were used as reference for developing polygonal meshes (PM) in 3DsMax to accurately render the cellular and organelle geometry. Absorbed doses to the nucleus per decay (S values) were calculated for 3 cellular morphologies: spheres (MIRDcell), truncated cone-shaped constructive solid geometry (CSG within MCNP6.1), and realistic PM models, using Geant4-10.03. The geometrical setup of the clonogenic survival assays was modeled, including dynamic changes in proliferation, proximity variations, and cell death. The absorbed dose to the nucleus by the radioactive source cell (self-dose) and surrounding source cells (cross-dose) was calculated applying the MIRD formalism. Finally, the correlation between absorbed dose and survival fraction was fitted using a linear dose-response curve (high α/β or fast sub-lethal damage repair half-life) for different assumptions, related to cellular shape and localization of the internalized fraction of activity. Results: The cross-dose, depending on cell proximity and colony formation, is a minor (15%) contributor to the total absorbed dose. Cellular volume (inverse exponential trend), shape modeling (up to 65%), and internalized source localization (up to + 149% comparing cytoplasm to Golgi) significantly influence the self-dose to nucleus. The absorbed dose delivered to the nucleus during a clonogenic survival assay is 3-fold higher with MIRDcell compared to the polygonal mesh structures. Our cellular dosimetry model indicates that 177 Lu-DOTATATE treatment might be more effective than suggested by average spherical cell dosimetry, predicting a lower absorbed dose for the same cellular survival. Dose-rate effects and heterogeneous dose delivery might account for differences in dose-response compared to x-ray irradiation.

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Section: Discussionmentioning

confidence: 99%

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

et al. 2020

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“…To advance toward microdosimetry and improved biophysical models, the spatial distribution of the radiopharmaceutical in the culture medium should be completed by evaluation of the subcellular distribution. The imaging techniques described here to determine the cells thickness, could be expanded to fluorescence tagged antibodies of VCAM‐1 to provide the activity distribution as a function of depth in the cell layer.…”

Section: Discussionmentioning

confidence: 99%

Radionuclide spatial distribution and dose deposition for in vitro assessments of ²¹²Pb‐αVCAM‐1 targeted alpha therapy

et al. 2020

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Purpose Targeted alpha therapy (TAT) takes advantage of the short‐range and high‐linear energy transfer of α‐particles and is increasingly used, especially for the treatment of metastatic lesions. Nevertheless, dosimetry of α‐emitters is challenging for the very same reasons, even for in vitro experiments. Assumptions, such as the uniformity of the distribution of radionuclides in the culture medium, are commonly made, which could have a profound impact on dose calculations. In this study we measured the spatial distribution of α‐emitting 212Pb coupled to an anti‐VCAM‐1 antibody (212Pb‐αVCAM‐1) and its evolution over time in the context of in vitro irradiations. Methods Two experimental setups were implemented without cells to measure α‐particle count rates and energy spectra in culture medium containing 15 kBq of 212Pb‐α‐VCAM‐1. Silicon detectors were placed above and below cell culture dishes for 20 h. One of the dishes had a 2.5‐µm‐thick mylar‐base allowing easy detection of the α‐particles. Monte Carlo simulations were performed to analyze experimental spectra. Experimental setups were modeled and α‐energy spectra were simulated in the silicon detectors for different decay positions in the culture medium. Simulated spectra were then used to deconvolute experimental spectra to determine the spatial distribution of 212Pb‐αVCAM‐1 in the medium. This distribution was finally used to calculate the dose deposition in cell culture experiments. Results Experimental count rates and energy spectra showed differences in measurements taken at the top and the bottom of dishes and temporal variations that did not follow 212Pb decay. The radionuclide spatial distribution was shown to be composed of a uniform distribution and concentration gradients at the top and the bottom, which were subjected to temporal variations that may be explained by gravity and electrostatic attraction. The absorbed dose in cells calculated from this distribution was compared with the dose expected for a uniform and static distribution and found to be 1.75 times higher, which is highly significant to interpret biological observations. Conclusions This study demonstrated that accurate dosimetry of α‐emitters requires the experimental determination of radionuclide spatial and temporal distribution and highlighted that in vitro assessment of dose for TAT cannot only rely on a uniform distribution of activity in the culture medium. The reliability and reproducibility of future experiments should benefit from specifically developed dosimetry tools and methods.

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“…The observed results, however, demonstrate that these discrepancies have a negligibly minor impact on the estimation of the absorbed dose to the cell nucleus. However, at the cellular and subcellular levels, using accurate cellular elemental composition and density is significant in dosimetry [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

A Monte Carlo study of the Cellular Dosimetry for SNCT Comparison with MIRD S Values

Zhang,

Lan,

Jiang

et al. 2023

Preprint

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Background An interesting isotope, sulfur-33 (a stable isotope), has been proposed as an additional neutron capture or a cooperating target for enhancing boron neutron capture therapy. Recently, 33S was considered as the substitute for boron-10 in neutron capture radiotherapy. The 33S (n, α)30Si reaction emits the α particles useful for neutron capture therapy. Based on the Monte Carlo method, we investigated the dosimetric characteristics of the cellular model of several geometries for the sulfur-33 neutron capture therapy (SNCT). Methods Monte Carlo N-Particle (MCNP) was used for simulating the transport of α particles emitted by SNCT from the cellular model surface (CS), cytoplasm (Cy), or nucleus (N) of a single cell model. The model cells were defined as two concentric spheres consisting of the nucleus and cytoplasm. The radius of the cell model was Rc=6 µm Rn=3 µm. The S values (SC←C, SC←CS, SN←N, SN←Cy, SN←CS) were compared to the results with the Medical Internal Radiation Dosimetry (MIRD) method. Finally, S values of the cellular model of several geometries were calculated. Results The relative differences of MCNP versus MIRD method S values for SNCT ranged from 0.28% to 4.29% for C to C (SC←C), -2.82% to 0.05% for Cs to C (SC←Cs), 0.54% to 4.42% for N to N (SN←N), 0.72% to 3.14% for Cy to N (SN ←Cy), and -1.76% to 0.36% for CS to N (SN←CS). The ratios of SN←N/ SC←C, SN←CS/SC←C, SN←Cy/ SC←C decreased with increasing the cell and nucleus size. Conclusion The S value simulated by MCNP is in agreement with the MIRD method, which is proved to be reliable for the cellular dosimetry of SNCT by the Monte Carlo method. The Model Carlo method can be used instead of the MIRD method to accurately calculate cellular S values, which solves the problem of cell shape limitation in MIRD method (which is suitable for regular spherical cellular model).

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Cellular dosimetry of different radionuclides for targeted radionuclide therapy: Monte Carlo simulation

Cited by 4 publications

References 34 publications

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

Radionuclide spatial distribution and dose deposition for in vitro assessments of ²¹²Pb‐αVCAM‐1 targeted alpha therapy

A Monte Carlo study of the Cellular Dosimetry for SNCT Comparison with MIRD S Values

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Cellular dosimetry of different radionuclides for targeted radionuclide therapy: Monte Carlo simulation

Cited by 4 publications

References 34 publications

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

Radionuclide spatial distribution and dose deposition for in vitro assessments of 212Pb‐αVCAM‐1 targeted alpha therapy

A Monte Carlo study of the Cellular Dosimetry for SNCT Comparison with MIRD S Values

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Radionuclide spatial distribution and dose deposition for in vitro assessments of ²¹²Pb‐αVCAM‐1 targeted alpha therapy