Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro
gráficas, ilustraciones, tablas
- Autores:
-
Londoño Tobon, Angela María
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/80291
- Palabra clave:
- 530 - Física
Nanopartículas
Factor de incremento de dosis (DEF)
Geant4 radio- terapia
Nanoparticles
Dose enhancement factor
Geant4
Radiotherapy
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
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| dc.title.spa.fl_str_mv |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| dc.title.translated.eng.fl_str_mv |
Study of the dosimetric characteristics of an external beam therapy with photons and gadolinium and gold nanoparticles. |
| title |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| spellingShingle |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro 530 - Física Nanopartículas Factor de incremento de dosis (DEF) Geant4 radio- terapia Nanoparticles Dose enhancement factor Geant4 Radiotherapy |
| title_short |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| title_full |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| title_fullStr |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| title_full_unstemmed |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| title_sort |
Estudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oro |
| dc.creator.fl_str_mv |
Londoño Tobon, Angela María |
| dc.contributor.advisor.none.fl_str_mv |
Castro Serrato, Héctor Fabio |
| dc.contributor.author.none.fl_str_mv |
Londoño Tobon, Angela María |
| dc.contributor.researchgroup.spa.fl_str_mv |
CRYOMAG y Física Médica |
| dc.subject.ddc.spa.fl_str_mv |
530 - Física |
| topic |
530 - Física Nanopartículas Factor de incremento de dosis (DEF) Geant4 radio- terapia Nanoparticles Dose enhancement factor Geant4 Radiotherapy |
| dc.subject.proposal.spa.fl_str_mv |
Nanopartículas Factor de incremento de dosis (DEF) Geant4 radio- terapia |
| dc.subject.proposal.eng.fl_str_mv |
Nanoparticles Dose enhancement factor Geant4 Radiotherapy |
| description |
gráficas, ilustraciones, tablas |
| publishDate |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2021-09-24T04:04:08Z |
| dc.date.available.none.fl_str_mv |
2021-09-24T04:04:08Z |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
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info:eu-repo/semantics/masterThesis |
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info:eu-repo/semantics/acceptedVersion |
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Text |
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http://purl.org/redcol/resource_type/TM |
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acceptedVersion |
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https://repositorio.unal.edu.co/handle/unal/80291 |
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Universidad Nacional de Colombia |
| dc.identifier.reponame.spa.fl_str_mv |
Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
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https://repositorio.unal.edu.co/handle/unal/80291 https://repositorio.unal.edu.co/ |
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Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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spa |
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spa |
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[1] “World Health Organization,” Sep. 12, 2018. https://www.who.int/news-room/fact-sheets/detail/cancer (accessed Jun. 13, 2020). [2] Globocan 2018, “Cancer today.” [3] F. Bray, A. Znaor, P. Cueva, and Col, Planificación y Desarrollo de registros de cáncer de base poblacional en los países de ingresos bajos y medios, vol. 43. 2015. [4] C. Elith, S. E. Dempsey, N. Findlay, and H. M. Warren-Forward, “An introduction to the intensity-modulated radiation therapy (IMRT) techniques, tomotherapy, and VMAT,” J. Med. Imaging Radiat. Sci., vol. 42, no. 1, pp. 37–43, 2011, doi: 10.1016/j.jmir.2010.11.005. [5] F. Moradi, K. Rezaee Ebrahim Saraee, S. F. Abdul Sani, and D. A. Bradley, “Metallic nanoparticle radiosensitization: The role of Monte Carlo simulations towards progress,” Radiat. Phys. Chem., vol. 180, p. 109294, 2021, doi: 10.1016/j.radphyschem.2020.109294. [6] A. V. Mesa, A. Norman, T. D. Solberg, J. J. Demarco, and J. B. Smathers, “Dose distributions using kilovoltage x-rays and dose enhancement from iodine contrast agents,” Phys. Med. Biol., vol. 44, no. 8, pp. 1955–1968, 1999, doi: 10.1088/0031-9155/44/8/308. [7] F. A. Geser, “Caracterización dosimétrica y monitoreo in situ para hadronterapia .,” 2019. [8] Fernando Rivas Navarro, “Recidiva anastomótica post-neoadyuvancia en cáncer de recto: correlación clínico-patológica,” La teisis Dr. en Teor. y Empir., p. 146, 2014. [9] J. Bernier, E. J. Hall, and A. Giaccia, “Radiation oncology: A century of achievements,” Nat. Rev. Cancer, vol. 4, no. 9, pp. 737–747, 2004, doi: 10.1038/nrc1451. [10] V. Á. Ramírez Agudelo, “Estudio de Factibilidad para la Unidad de Radioterapia del Centro Oncológico de Antioquia S.A.,” p. 75, 2014. [11] A. Sam Beddar et al., “Intraoperative radiation therapy using mobile electron linear accelerators: Report of AAPM Radiation Therapy Committee Task Group No. 72,” Med. Phys., vol. 33, no. 5, pp. 1476–1489, 2006, doi: 10.1118/1.2194447. [12] V. M. Muñoz, G. Gil, and P. Nigorra, “100 Años De Radioterapia,” pp. 130–138, 1898, [Online]. Available: http://ibdigital.uib.es/greenstone/collect/medicinaBalear/import/1995_v10_n3/Medicina_Balear_1995v10n3p130.pdf. [13] L. Torres, “Las radiaciones en la vida cotidiana,” p. 245, 2017. [14] N. York, “Los radioisótopos en el tratamiento de cáncer,” pp. 25–27. [15] L. T. D. L. Á. R. PAREDES, “INFLUENCIA DE LA COMUNICACIÓN DEL PROFESIONAL EN RADIOLOGÍA CON EL EQUIPO MULTIDISCIPLINARIO EN EL SERVICIO DE RADIOTERAPIA SOBRE LA PROTECCIÓN RADIOLÓGICA A LOS PACIENTES TRATADOS EN EL ÁREA DE TELETERAPIA, HOSPITAL MÉDICO QUIRÚRGICO Y ONCOLÓGICO DEL INS,” Angew. Chemie Int. Ed. 6(11), 951–952., 2017. [16] “Papel de la radioterapia en el siglo XXI.” https://scielo.isciii.es/scielo.php?script=sci_arttext&pid=S1137-66272009000400001 (accessed Jul. 29, 2021). [17] U. of M. M. C. Benedick A.Fraass(Departament of Radiation Oncology, “the development of conformal radiation therapy.” [18] J. Switon and G. G. Hill, “Clinical oncology,” W.B. Saunders Co., Philadelphia, vol. m, pp. 288–296, 1977, doi: 10.5858/2001-125-582b-co. [19] A. S. V., “Radioterapia de intensidad modulada (IMRT),” Rev. Médica Clínica Las Condes, vol. 22, no. 6, pp. 834–843, 2011, doi: 10.1016/s0716-8640(11)70496-5. [20] C. X. Yu, “Intensity-modulated arc therapy with dynamic multileaf collimation: An alternative to tomotherapy,” Phys. Med. Biol., vol. 40, no. 9, pp. 1435–1449, 1995, doi: 10.1088/0031-9155/40/9/004. [21] D. A. Palma, W. F. A. R. Verbakel, K. Otto, and S. Senan, “New developments in arc radiation therapy: A review,” Cancer Treat. Rev., vol. 36, no. 5, pp. 393–399, 2010, doi: 10.1016/j.ctrv.2010.01.004. [22] T. Bortfeld, “Optimized planning using physical objectives and constraints,” Semin. Radiat. Oncol., vol. 9, no. 1, pp. 20–34, 1999, doi: 10.1016/S1053-4296(99)80052-6. [23] L. Cetina, T. Wegman, A. García-Arias, M. Candelaria, A. Dueñas-González, and 1, “Radiosensibilizantes En Cáncer Cérvicouterino,” Inst. Nac. Cancerol. Mex., vol. 22, pp. 4–29, 2006, [Online]. Available: http://www.incan.org.mx/revistaincan/elementos/documentosPortada/1172192290.pdf. [24] D. M. Herold, I. J. Das, C. C. Stobbe, R. V. Iyer, and J. D. Chapman, “Gold microspheres: A selective technique for producing biologically effective dose enhancement,” Int. J. Radiat. Biol., vol. 76, no. 10, pp. 1357–1364, 2000, doi: 10.1080/09553000050151637. [25] Z. Kuncic and S. Lacombe, “Nanoparticle radio-enhancement: Principles, progress and application to cancer treatment,” Phys. Med. Biol., vol. 63, no. 2, 2018, doi: 10.1088/1361-6560/aa99ce. [26] I. Miladi et al., “The in vivo radiosensitizing effect of gold nanoparticles based mri contrast agents,” Small, vol. 10, no. 6, pp. 1116–1124, 2014, doi: 10.1002/smll.201302303. [27] N. Su, Y. Dang, G. Liang, and G. Liu, “Iodine-125-labeled cRGD-gold nanoparticles as tumor-targeted radiosensitizer and imaging agent,” Nanoscale Res. Lett., vol. 10, no. 1, 2015, doi: 10.1186/s11671-015-0864-9. [28] T. Wolfe et al., “Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo,” Nanomedicine Nanotechnology, Biol. Med., vol. 11, no. 5, pp. 1277–1283, 2015, doi: 10.1016/j.nano.2014.12.016. [29] Y. Dou et al., “Size-Tuning Ionization to Optimize Gold Nanoparticles for Simultaneous Enhanced CT Imaging and Radiotherapy,” ACS Nano, vol. 10, no. 2, pp. 2536–2548, 2016, doi: 10.1021/acsnano.5b07473. [30] J. L. Bridot et al., “Hybrid gadolinium oxide nanoparticles: Multimodal contrast agents for in vivo imaging,” J. Am. Chem. Soc., vol. 129, no. 16, pp. 5076–5084, 2007, doi: 10.1021/ja068356j. [31] S. Dufort et al., “The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors,” Sci. Rep., vol. 6, no. June, pp. 1–8, 2016, doi: 10.1038/srep29678. [32] A. Detappe et al., “Key clinical beam parameters for nanoparticle-mediated radiation dose amplification,” Sci. Rep., vol. 6, no. June, pp. 1–8, 2016, doi: 10.1038/srep34040. [33] A. Detappe et al., “Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy,” J. Control. Release, vol. 238, pp. 103–113, 2016, doi: 10.1016/j.jconrel.2016.07.021. [34] H. Alejo-Martinez, A. C. Sevilla-Moreno, A. Ondo-Mendéz, J. H. Quintero, and C. J. Páez, “Comparison of Bi 2 S 3 and Ta 2 O 5 as alternative materials to gold in nanoparticles used as agents to increase the dose in radiotherapy,” J. Phys. Conf. Ser., vol. 1247, no. 1, 2019, doi: 10.1088/1742-6596/1247/1/012050. [35] A. K. Rath and N. Sahoo, Particle radiotherapy: Emerging technology for treatment of cancer. 2016. [36] M. Hossain and M. Su, “Nanoparticle location and material-dependent dose enhancement in X-ray radiation therapy,” J. Phys. Chem. C, vol. 116, no. 43, pp. 23047–23052, 2012, doi: 10.1021/jp306543q. [37] Cunningham, “The Physics of Radiology 4th ed - H. Johns, J. Cunningham (Charles Thomas, 1983),” A monograph in the bannerstone Division of American lectures in radiation theraphy. 1983. [38] S. Cherry, J. Sorenson, and M. Phelps, Physics in Nuclear Medicine. 2012. [39] J. J. M. B. jerrold T.Bushberg, J.Anthony Seibert, Edwin M.leidholdt, The Essential Physics of Medical Imaging, Third edit. 2010. [40] A. A. Ridha, “(PDF) Chapter Four (Interaction of Radiation with Matter),” no. September, 2016, [Online]. Available: https://www.researchgate.net/publication/307588101_Chapter_Four_Interaction_of_Radiation_with_Matter. [41] E.B.Podgorsak, Radiaiton oncology physics, vol. 52, no. 20. 2005. [42] T. Page, E. Loss, and I. Scattering, “Fundamentals of ionizing radiation dosimetry - Pedro Andreo.” [43] E. J. Hall and S. Willson, Radiobiology for thr radiologist, 7th ed. . [44] E. B. Podgorsak., “Radiation Physics for Medical Physicists. Biological and Medical Physics, Biomedical Engineering.,” Springer Berlin Heidelberg, Berlin, Heidelb., 2010. [45] “XCOM: Element Options.” https://physics.nist.gov/cgi-bin/Xcom/xcom2 (accessed Nov. 16, 2020). [46] ICRU Report 37, on Radiation Units and Measurements Icru Report 37. 1984. [47] S. Incerti et al., “THE Geant4-DNA project,” Int. J. Model. Simulation, Sci. Comput., vol. 1, no. 2, pp. 157–178, 2010, doi: 10.1142/S1793962310000122. [48] G.-D. COLLABORATION, “Geant4-DNA.” http://geant4-dna.org/. [49] M. P. Little, “Risks associated with ionizing radiation,” Br. Med. Bull., vol. 68, no. May, pp. 259–275, 2003, doi: 10.1093/bmb/ldg031. [50] Pianetta Piero, “Section 3-2 Electron Ranges in Matter,” . [51] K. T. Butterworth, S. J. McMahon, F. J. Currell, and K. M. Prise, “Physical basis and biological mechanisms of gold nanoparticle radiosensitization,” Nanoscale, vol. 4, no. 16, pp. 4830–4838, 2012, doi: 10.1039/c2nr31227a. [52] S. D. Perrault, C. Walkey, T. Jennings, H. C. Fischer, and W. C. W. Chan, “Mediating tumor targeting efficiency of nanoparticles through design,” Nano Lett., vol. 9, no. 5, pp. 1909–1915, 2009, doi: 10.1021/nl900031y. [53] E. Herranz, “Simulaciones Monte Carlo para Radioterapia Intraoperatoria con haces de electrones,” Dep. Física Atómica, Mol. y Nucl., vol. Doctorado, 2013. [54] “Stopping Power and Range Tables for Electrons.” https://physics.nist.gov/cgi-bin/Star/e_table.pl (accessed Jan. 05, 2021). [55] S. Her, D. A. Jaffray, and C. Allen, “Gold nanoparticles for applications in cancer radiotherapy: Mechanisms and recent advancements,” Adv. Drug Deliv. Rev., vol. 109, pp. 84–101, 2017, doi: 10.1016/j.addr.2015.12.012. [56] E. A. Sykes, J. Chen, G. Zheng, and W. C. W. Chan, “Investigating the impact of nanoparticle size on active and passive tumor targeting efficiency,” ACS Nano, vol. 8, no. 6, pp. 5696–5706, 2014, doi: 10.1021/nn500299p. [57] L. Y. T. Chou and W. C. W. 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Sci., vol. 19, no. 9, 2018, doi: 10.3390/ijms19092790. [66] C. Zhou, M. Long, Y. Qin, X. Sun, and J. Zheng, “Luminescent gold nanoparticles with efficient renal clearance,” Angew. Chemie - Int. Ed., vol. 50, no. 14, pp. 3168–3172, 2011, doi: 10.1002/anie.201007321. [67] W. S. Cho et al., “Size-dependent tissue kinetics of PEG-coated gold nanoparticles,” Toxicol. Appl. Pharmacol., vol. 245, no. 1, pp. 116–123, 2010, doi: 10.1016/j.taap.2010.02.013. [68] Fernández Almudena, “Aplicaciones de la nanomedicina para el diagnóstico y tratamiento del cáncer de mama,” pp. 1–19, 2017. [69] “ROOT.” https://root.cern/about/ (accessed Jul. 15, 2021). [70] S. Agostinelli et al., “GEANT4 - A simulation toolkit,” Nucl. Instruments Methods Phys. Res. Sect. A Accel. Spectrometers, Detect. Assoc. Equip., vol. 506, no. 3, pp. 250–303, 2003, doi: 10.1016/S0168-9002(03)01368-8. [71] “Overview | geant4.web.cern.ch.” https://geant4.web.cern.ch/node/1 (accessed Mar. 14, 2021). [72] “Low Energy Electromagnetic Physics - Livermore | geant4.web.cern.ch.” https://geant4.web.cern.ch/node/1619 (accessed Mar. 14, 2021). [73] “Physics List.” http://geant4-dna.in2p3.fr/styled-3/styled-9/index.html (accessed Mar. 03, 2021). [74] M. H. and M. Su, “Influence of concentration, nanoparticle size, beam energy, and material on dose enhancemnt i radiation therapy.” Journal if radiation research, Oxford, 2017. |
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Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Castro Serrato, Héctor Fabio8746f6e67a0c6080ae1924c0c256d0a8Londoño Tobon, Angela María2796c0d50db30c216a64e7824d445220CRYOMAG y Física Médica2021-09-24T04:04:08Z2021-09-24T04:04:08Z2021https://repositorio.unal.edu.co/handle/unal/80291Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/gráficas, ilustraciones, tablasLa radioterapia es un tratamiento del cáncer, donde se utiliza radiación ionizante con el fin de destruir el tejido tumoral y proteger el tejido sano tanto como sea posible. El propósito de este trabajo fue analizar los efectos del material, tamaño y concentración de nanopartículas de alto número atómico utilizadas como agentes de incremento de dosis (radio-sensibilizantes) en el rango de energías de keV a MV. Para rayos X de baja energía la interacción dominante es el efecto fotoeléctrico, el cual implica la absorción de un fotón y posteriormente la producción de fotoelectrones, rayos X característicos y electrones Auger. Se construyoóuna simulación Monte Carlo basada en Geant 4 donde se utilizaron materiales de alto número atómico: Au, Gd, Pt, Bi2S3, Ta2O5, espectros de energía para voltaje del tubo de RX de: 40, 100, 180 kVp y 6 MV y diferentes tamaños de nanopartículas. Se analizaron los procesos de interacción radiación materia, se calculó la energía depositada, dosis absorbida, el factor de incremento de dosis generados por los electrones secundarios por la interacción de 2 millones de fotones incidentes en las nanopartículas. Se realizo variación en la concentración de las nanopartículas y se analizó el factor de incremento de dosis. Pese a que para una sola nanopartícula los efectos de mejora de dosis ocurren para nanopartcíulas con mayor Z (Au, Pt), de mayor tamaño a la m ínima energ ía 40 kVp, sin embargo, cuando se tiene una concentración en peso de nanopartículas, se encuentra que el incremento de dosis es proporcional a la concentración, independiente de Z, siendo mayor el efecto a menor energíıa (40 KeV). Para energíıas en el rango de MeV, el incremento de dosis hallado es casi despreciable. Se concluye que los valores óptimos del tamaño de las nanopartículas y su concentración, siendo el máximo posible, estos valores han de determinarse de acuerdo con otros criterios, como la toxicidad, biocompatibilidad, etc. Por tal razón los parámetros óptimos escogidos fueron tamaño de nanopartícula de 20 nm, energía de 40 keV para materiales (Au y Pt), Se observó un incremento de dosis de forma radial dentro de los 300 nm desde la superficie de la nanopartícula, lo que causa un mayor efecto de destrucción de células en tejido maligno y protege el tejido sano, en comparación con el tratamiento sin nanopartículas por tal razón físicamente hay una mejora de dosis al introducir nanopartículas de alto Z. (Texto tomado de la fuente)Radiotherapy is an essential component in the treatment of all types of cancer, in which ionizing radiation is used to destroy tumor tissue, protecting healthy tissue as much as possible. The purpose of this work was to analyze the effects of material, size, and concentration of high atomic number nanoparticles used as a radio-sensitization agent in a range of energies from keV to MeV. For low energy x-rays the dominant interaction is the photoelectric effect, which involves the absorption of a photon and subsequently the production of photoelectrons, characteristic X-rays and Auger electrons. A Monte Carlo simulation based on Geant 4 was built using high atomic number materials: Au, Gd, Pt, Bi2S3, Ta2O5, different energy spectra for X-Ray tube voltages: 40, 100, 180 kVp, and 6 MV, and different sizes of nanoparticles. The radiation-matter interaction processes were analyzed, the deposited energy, absorbed dose, the dose increase factor due to the secondary electrons generated by the interaction of 2 million photons incident in the nanoparticles,Variation in nanoparticle concentration was performed and the dose enhancement factor was analyzed. Although for a single nanoparticle the dose enhancement effects occur for nanoparticles with higher Z (Au, Pt), of larger size at the minimum energy 40 kVp, however, when there is a concentration in weight of nanoparticles, it is found that the dose increase is proportional to the concentration, independent of Z, being greater the effect at lower energy (40 kVp). For energies in the MV range, the dose increase found is almost negligible. It is concluded that the optimal values of nanoparticle size and concentration, being the maximum possible, these values have to be determined according with other criteria, such as toxicity, biocompatibility, etc. For this reason the optimal parameters chosen were nanoparticle size of 20 nm, energy of 40 kVp for materials (Au and Pt). A radial dose increase was observed within 300 nm from the surface of the nanoparticle, which causes a greater effect of destruction of cells in malignant tissue and protects healthy tissue, compared to the treatment without nanoparticles for this reason physically there is a dose improvement when introducing high Z nanoparticles.MaestríaMagíster en Física MédicaRadioterapia89 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Física MédicaDepartamento de FísicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá530 - FísicaNanopartículasFactor de incremento de dosis (DEF)Geant4 radio- terapiaNanoparticlesDose enhancement factorGeant4RadiotherapyEstudio de las características dosimétricas de un haz de terapia externa con fotones y nanopartículas de gadolinio y oroStudy of the dosimetric characteristics of an external beam therapy with photons and gadolinium and gold nanoparticles.Trabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM[1] “World Health Organization,” Sep. 12, 2018. https://www.who.int/news-room/fact-sheets/detail/cancer (accessed Jun. 13, 2020). 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Su, “Influence of concentration, nanoparticle size, beam energy, and material on dose enhancemnt i radiation therapy.” Journal if radiation research, Oxford, 2017.Público generalORIGINAL1061763025.2021.pdf1061763025.2021.pdfMaestría en Física Médicaapplication/pdf2548916https://repositorio.unal.edu.co/bitstream/unal/80291/4/1061763025.2021.pdf025dbdc88ab47ddd16ede8abff226aaeMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-83964https://repositorio.unal.edu.co/bitstream/unal/80291/3/license.txtcccfe52f796b7c63423298c2d3365fc6MD53THUMBNAIL1061763025.2021.pdf.jpg1061763025.2021.pdf.jpgGenerated Thumbnailimage/jpeg5042https://repositorio.unal.edu.co/bitstream/unal/80291/5/1061763025.2021.pdf.jpgb29780337bf7fdb93b74a6b81727ec3fMD55unal/80291oai:repositorio.unal.edu.co:unal/802912023-07-28 23:04:02.522Repositorio Institucional Universidad Nacional de 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