Dosimetry of brachytherapy using radioactive nanoparticles: in silico
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/36710 https://orcid.org/0000-0001-8250-5982 |
Resumo: | Radioactive nanoparticles (radio-NPs) functionalized with tumor specific biomolecules, injected intratumorally, have been reported as an alternative to low dose rate (LDR) seed based brachytherapy (BT). In radiation based cancer treatments accurate estimation of absorbed dose is crucial for proper disease control and to minimize the risk of radiation induced side effects. Currently, used Medical Internal Radiation Dose (MIRD) formalism for internal dosimetry purposes do not consider the impact of uptake and washout of radiopharmaceutical on the cell survival fraction (SF) and absorbed dose estimation. The single cell dosimetry (SCD), based on MIRD formalism, is generally used to evaluate the dosimetric characteristics of radionuclides for theranostic applications. However, there exists discrepancies in the graphical methods and radial energy distribution, used to estimate the dose distribution. Moreover, precise modeling of radiation transport in the medium by Monte Carlo (MC) codes plays a pivotal role in the estimation of absorbed dose. The dose point kernel (DPK) are used to: (i) test the accuracy of different Monte Carlo (MC) codes, by performing comparison in terms of DPK; and (ii) estimate 3D-absorbed dose in nuclear medicine. However, as per our knowledge the impact differences in DPK on absorbed dose was not investigated. This PhD project aims to perform dosimetry of LDR BT applications, using radio-NPs, and fill the above mentioned gaps in literature using MC methods. The dosimetric calculations were performed using two widely used MC codes: Geant4-DNA and EGSnrc. Initially, the comparison in terms of DPK for electrons in energy range of 1 keV to 3 MeV was made to test the accuracy of both codes. After validation, SCD approach was used to evaluate the dosimetric characteristics of 12 alpha/beta/auger emitting radionuclides for theranostic applications. The concept of radial dose function was also proposed for graphical representation of dose distribution. Further, the cell survival curves published in literature were replicated using the mathematical model proposed by Sefl et al. 2016. Our findings show that, both Geant4-DNA and EGSnrc can accurately simulate the transport of low energy electrons with respect to other MC codes. Moreover, the largest differences between DPKs were found for electron energies below 10 keV, which resulted in inhomogeneous dose distribution in micrometer and no impact on millimeter sized voxels. The alpha emitters were found to deposit highest absorbed dose in comparison to auger and beta emitters. Furthermore, we effectively replicated the cell survival curves published in literature on the use of radio-NPs for LDR BT applications. It was concluded that the accuracy of the MC codes and MC parameters must be validated and benchmarked before using them for dosimetry purposes. Also, the accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumour repopulation rate is important for the calculation of cell survival curves. |
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Telma Cristina Ferreira Fonsecahttp://lattes.cnpq.br/3139727297057976Jan SchuemannTarcísio Passos Ribeiro de CamposRalph Santos OliveiraBruno Melo MendesLucas Freitas de FreitasLuc Beaulieuhttp://lattes.cnpq.br/8256803192379960Baljeet Seniwal2021-07-12T17:16:33Z2021-07-12T17:16:33Z2021-05-10http://hdl.handle.net/1843/36710https://orcid.org/0000-0001-8250-5982Radioactive nanoparticles (radio-NPs) functionalized with tumor specific biomolecules, injected intratumorally, have been reported as an alternative to low dose rate (LDR) seed based brachytherapy (BT). In radiation based cancer treatments accurate estimation of absorbed dose is crucial for proper disease control and to minimize the risk of radiation induced side effects. Currently, used Medical Internal Radiation Dose (MIRD) formalism for internal dosimetry purposes do not consider the impact of uptake and washout of radiopharmaceutical on the cell survival fraction (SF) and absorbed dose estimation. The single cell dosimetry (SCD), based on MIRD formalism, is generally used to evaluate the dosimetric characteristics of radionuclides for theranostic applications. However, there exists discrepancies in the graphical methods and radial energy distribution, used to estimate the dose distribution. Moreover, precise modeling of radiation transport in the medium by Monte Carlo (MC) codes plays a pivotal role in the estimation of absorbed dose. The dose point kernel (DPK) are used to: (i) test the accuracy of different Monte Carlo (MC) codes, by performing comparison in terms of DPK; and (ii) estimate 3D-absorbed dose in nuclear medicine. However, as per our knowledge the impact differences in DPK on absorbed dose was not investigated. This PhD project aims to perform dosimetry of LDR BT applications, using radio-NPs, and fill the above mentioned gaps in literature using MC methods. The dosimetric calculations were performed using two widely used MC codes: Geant4-DNA and EGSnrc. Initially, the comparison in terms of DPK for electrons in energy range of 1 keV to 3 MeV was made to test the accuracy of both codes. After validation, SCD approach was used to evaluate the dosimetric characteristics of 12 alpha/beta/auger emitting radionuclides for theranostic applications. The concept of radial dose function was also proposed for graphical representation of dose distribution. Further, the cell survival curves published in literature were replicated using the mathematical model proposed by Sefl et al. 2016. Our findings show that, both Geant4-DNA and EGSnrc can accurately simulate the transport of low energy electrons with respect to other MC codes. Moreover, the largest differences between DPKs were found for electron energies below 10 keV, which resulted in inhomogeneous dose distribution in micrometer and no impact on millimeter sized voxels. The alpha emitters were found to deposit highest absorbed dose in comparison to auger and beta emitters. Furthermore, we effectively replicated the cell survival curves published in literature on the use of radio-NPs for LDR BT applications. It was concluded that the accuracy of the MC codes and MC parameters must be validated and benchmarked before using them for dosimetry purposes. Also, the accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumour repopulation rate is important for the calculation of cell survival curves.Nanopartículas radioativas (radio-NPs) funcionalizadas com biomoléculas específicas do tumor, injetadas de forma intratumoral, têm sido relatadas como uma alternativa à braquiterapia à base de sementes (LDR) de baixa taxa de dose (LDR). Em tratamentos de câncer à base de radiação a estimativa precisa da dose absorvida é crucial para o controle adequado da doença e para minimizar o risco de efeitos colaterais induzidos por radiação. Atualmente, o formalismo da Dose de Radiação Interna Médica (MIRD) usado para fins de dosimetria interna não considera o impacto da absorção e lavagem de radiofarmacêuticos na fração de sobrevivência celular (FS) e estimativa de dose absorvida. A dosimetria celular única (SCD), baseada no formalismo MIRD, é geralmente usada para avaliar as características dosimétricas dos radionuclídeos para aplicações teranósticas. No entanto, existem discrepâncias nos métodos gráficos e na distribuição de energia radial, utilizadas para estimar a distribuição da dose. Além disso, a modelagem precisa do transporte de radiação no meio pelos códigos de Monte Carlo (MC) desempenha um papel fundamental na estimativa da dose absorvida. O núcleo de ponto de dose (DPK) é usado para: (i) testar a precisão de diferentes códigos de Monte Carlo (MC), realizando comparação em termos de DPK; e (ii) estimam a dose absorvida por 3D na medicina nuclear. No entanto, pelo que sabemos, não foram investigadas as diferenças de impacto na DPK na dose absorvida. Este projeto de doutorado tem como objetivo realizar a dosimetria de aplicações LDR BT, utilizando radio-NPs, e preencher as lacunas acima mencionadas na literatura usando métodos de Monte Carlo (MC). Os cálculos dosimétricos foram realizados utilizando-se dois códigos MC amplamente utilizados: Geant4-DNA e EGSnrc. Inicialmente, a comparação em termos de DPK para elétrons na faixa de energia de 1 keV a 3 MeV foram realizadas para testar a precisão de ambos os códigos. Após a validação, utilizou-se a abordagem SCD para avaliar as características dosimétricas de emissão dos radionuclídeos de 12 alfa/beta/auger para aplicações teranósticas. Também foi proposto o conceito de função de dose radial para representação gráfica da distribuição de doses. Além disso, as curvas de sobrevivência celular publicadas na literatura foram replicadas utilizando-se o modelo matemático proposto por Sefl et al. 2016. O nosso trabalho apresenta que, tanto o Geant4-DNA quanto o EGSnrc podem simular com precisão o transporte de elétrons de baixa energia em relação a outros códigos MC. Além disso, as maiores diferenças entre as DPKs foram encontradas para energias eletrônicas abaixo de 10 keV, o que resultou na distribuição de dose homogênea em micrômetros e sem impacto em voxels em tamanhos milimétricos. Os emissores alfas foram encontrados para depositar a dose mais alta absorvida em comparação com os emissores auger e beta. Além disso, replicamos efetivamente as curvas de sobrevivência celular publicadas na literatura sobre o uso de radio-NPs para aplicações LDR BT. Concluiu-se que a precisão dos códigos MC e parâmetros MC deve ser validada e referenciada antes de usá-los para fins de dosimetria. Além disso, o conhecimento preciso da taxa de absorção, taxa de lavagem de NPs, radio-sensibilidade e taxa de repopulação de tumores é importante para o cálculo das curvas de sobrevivência celular. Keywords: Braquiterapia LDR, nanopartículas radioativas, núcleos de ponto de dose, métodos de Monte Carlo.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências e Técnicas NuclearesUFMGBrasilENG - DEPARTAMENTO DE ENGENHARIA NUCLEAREngenharia nuclearBraquiterapiaMétodo de Monte CarloLDR brachytherapyRadioactive nanoparticlesDose point kernelsMonte Carlo methodsDosimetry of brachytherapy using radioactive nanoparticles: in silicoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/36710/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD52ORIGINALThesis_Baljeet.pdfThesis_Baljeet.pdfapplication/pdf9390827https://repositorio.ufmg.br/bitstream/1843/36710/1/Thesis_Baljeet.pdf032e1a1f89c845e5bc62ef1133fd4b0fMD511843/367102021-07-12 14:16:33.217oai:repositorio.ufmg.br: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ório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-07-12T17:16:33Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
title |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
spellingShingle |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico Baljeet Seniwal LDR brachytherapy Radioactive nanoparticles Dose point kernels Monte Carlo methods Engenharia nuclear Braquiterapia Método de Monte Carlo |
title_short |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
title_full |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
title_fullStr |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
title_full_unstemmed |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
title_sort |
Dosimetry of brachytherapy using radioactive nanoparticles: in silico |
author |
Baljeet Seniwal |
author_facet |
Baljeet Seniwal |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Telma Cristina Ferreira Fonseca |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3139727297057976 |
dc.contributor.advisor-co1.fl_str_mv |
Jan Schuemann |
dc.contributor.referee1.fl_str_mv |
Tarcísio Passos Ribeiro de Campos |
dc.contributor.referee2.fl_str_mv |
Ralph Santos Oliveira |
dc.contributor.referee3.fl_str_mv |
Bruno Melo Mendes |
dc.contributor.referee4.fl_str_mv |
Lucas Freitas de Freitas |
dc.contributor.referee5.fl_str_mv |
Luc Beaulieu |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8256803192379960 |
dc.contributor.author.fl_str_mv |
Baljeet Seniwal |
contributor_str_mv |
Telma Cristina Ferreira Fonseca Jan Schuemann Tarcísio Passos Ribeiro de Campos Ralph Santos Oliveira Bruno Melo Mendes Lucas Freitas de Freitas Luc Beaulieu |
dc.subject.por.fl_str_mv |
LDR brachytherapy Radioactive nanoparticles Dose point kernels Monte Carlo methods |
topic |
LDR brachytherapy Radioactive nanoparticles Dose point kernels Monte Carlo methods Engenharia nuclear Braquiterapia Método de Monte Carlo |
dc.subject.other.pt_BR.fl_str_mv |
Engenharia nuclear Braquiterapia Método de Monte Carlo |
description |
Radioactive nanoparticles (radio-NPs) functionalized with tumor specific biomolecules, injected intratumorally, have been reported as an alternative to low dose rate (LDR) seed based brachytherapy (BT). In radiation based cancer treatments accurate estimation of absorbed dose is crucial for proper disease control and to minimize the risk of radiation induced side effects. Currently, used Medical Internal Radiation Dose (MIRD) formalism for internal dosimetry purposes do not consider the impact of uptake and washout of radiopharmaceutical on the cell survival fraction (SF) and absorbed dose estimation. The single cell dosimetry (SCD), based on MIRD formalism, is generally used to evaluate the dosimetric characteristics of radionuclides for theranostic applications. However, there exists discrepancies in the graphical methods and radial energy distribution, used to estimate the dose distribution. Moreover, precise modeling of radiation transport in the medium by Monte Carlo (MC) codes plays a pivotal role in the estimation of absorbed dose. The dose point kernel (DPK) are used to: (i) test the accuracy of different Monte Carlo (MC) codes, by performing comparison in terms of DPK; and (ii) estimate 3D-absorbed dose in nuclear medicine. However, as per our knowledge the impact differences in DPK on absorbed dose was not investigated. This PhD project aims to perform dosimetry of LDR BT applications, using radio-NPs, and fill the above mentioned gaps in literature using MC methods. The dosimetric calculations were performed using two widely used MC codes: Geant4-DNA and EGSnrc. Initially, the comparison in terms of DPK for electrons in energy range of 1 keV to 3 MeV was made to test the accuracy of both codes. After validation, SCD approach was used to evaluate the dosimetric characteristics of 12 alpha/beta/auger emitting radionuclides for theranostic applications. The concept of radial dose function was also proposed for graphical representation of dose distribution. Further, the cell survival curves published in literature were replicated using the mathematical model proposed by Sefl et al. 2016. Our findings show that, both Geant4-DNA and EGSnrc can accurately simulate the transport of low energy electrons with respect to other MC codes. Moreover, the largest differences between DPKs were found for electron energies below 10 keV, which resulted in inhomogeneous dose distribution in micrometer and no impact on millimeter sized voxels. The alpha emitters were found to deposit highest absorbed dose in comparison to auger and beta emitters. Furthermore, we effectively replicated the cell survival curves published in literature on the use of radio-NPs for LDR BT applications. It was concluded that the accuracy of the MC codes and MC parameters must be validated and benchmarked before using them for dosimetry purposes. Also, the accurate knowledge of uptake rate, washout rate of NPs, radio-sensitivity and tumour repopulation rate is important for the calculation of cell survival curves. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-07-12T17:16:33Z |
dc.date.available.fl_str_mv |
2021-07-12T17:16:33Z |
dc.date.issued.fl_str_mv |
2021-05-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/36710 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0001-8250-5982 |
url |
http://hdl.handle.net/1843/36710 https://orcid.org/0000-0001-8250-5982 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências e Técnicas Nucleares |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ENG - DEPARTAMENTO DE ENGENHARIA NUCLEAR |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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