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Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy

PURPOSE: To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro‐level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha‐immuno‐conjugate and d...

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Autores principales: Xu, T., Liu, T., Li, G., Dugal, C., Aydemir, N. A., Liu, Y., Roeske, J. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384137/
https://www.ncbi.nlm.nih.gov/pubmed/32129888
http://dx.doi.org/10.1002/mp.14111
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author Xu, T.
Liu, T.
Li, G.
Dugal, C.
Aydemir, N. A.
Liu, Y.
Roeske, J. C.
author_facet Xu, T.
Liu, T.
Li, G.
Dugal, C.
Aydemir, N. A.
Liu, Y.
Roeske, J. C.
author_sort Xu, T.
collection PubMed
description PURPOSE: To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro‐level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha‐immuno‐conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro‐level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative. METHODS: A multi‐physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time‐dependent absorbed dose to the target. RESULTS: The conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. CONCLUSION: Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future.
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spelling pubmed-73841372020-07-28 Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy Xu, T. Liu, T. Li, G. Dugal, C. Aydemir, N. A. Liu, Y. Roeske, J. C. Med Phys COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY PURPOSE: To predict biological effects of targeted alpha therapy (TAT) in preclinical studies, dosimetry calculations based on the micro‐level distributions of emitters are essential. Due to the saturation of the tumor antigenic sites and bonding breaks by decay, some of Alpha‐immuno‐conjugate and decay daughters may inevitably be transported by convection and diffusion along with blood or lymphatic circulation. This results in highly nonuniform and unsteady distributions of irradiation sources. Since the micro‐level distribution of emitters cannot be measured and obtained in patients with current technology, a modeling toolset to give more insight of the internal dose could be an alternative. METHODS: A multi‐physics model based on a Monte Carlo microdosimetry technique and computational fluid dynamics (CFD) modeling was developed and applied to multiple internal irradiation sources. The CFD model tracks the path of the radionuclides and the dose model is capable of evaluating the time‐dependent absorbed dose to the target. RESULTS: The conceptual model is capable of handling complex nonuniform irradiation sources in vasculature. The results from the simulations indicate that the assumption of homogeneous and motionless distribution of the administered activity used in the conventional dose calculation tends to significantly underestimate or overestimate the absorbed dose to the vascular system in various scenarios. CONCLUSION: Modeling the in vivo transport of radionuclides has the potential to improve the accuracy of TAT dose estimates. It could be the first step to develop a simulation tool set for assessing absorbed dose to tumor or normal tissues and predict the corresponding biological responses in the future. John Wiley and Sons Inc. 2020-03-31 2020-06 /pmc/articles/PMC7384137/ /pubmed/32129888 http://dx.doi.org/10.1002/mp.14111 Text en © 2020 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY
Xu, T.
Liu, T.
Li, G.
Dugal, C.
Aydemir, N. A.
Liu, Y.
Roeske, J. C.
Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title_full Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title_fullStr Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title_full_unstemmed Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title_short Technical Note: The development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
title_sort technical note: the development of a multi‐physics simulation tool to estimate the background dose by systemic targeted alpha therapy
topic COMPUTATIONAL AND EXPERIMENTAL DOSIMETRY
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384137/
https://www.ncbi.nlm.nih.gov/pubmed/32129888
http://dx.doi.org/10.1002/mp.14111
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