Puesta apunto de la irradiación, control de la calidad radionucleídica y comportamiento de fantomas de microesferas de 32P para radioembolización / Fine-tuning of irradiation, control of radionuclide quality and behavior in phantoms of 32P radioembolization microspheres

Brühlmann, Santiago A. (2021) Puesta apunto de la irradiación, control de la calidad radionucleídica y comportamiento de fantomas de microesferas de 32P para radioembolización / Fine-tuning of irradiation, control of radionuclide quality and behavior in phantoms of 32P radioembolization microspheres. Proyecto Integrador Ingeniería Nuclear, Universidad Nacional de Cuyo, Instituto Balseiro.

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Resumen en español

El carcinoma hepatocelular (HCC) es uno de los principales factores de incidencia y mortalidad entre los cánceres de hígado, provocando anualmente más de medio millón de fallecidos a nivel mundial. La radioterapia intra-arterial selectiva (SIRT) utilizando microesferas (ME) con radioisótopos emisores β- puros puede obtener efectos paliativos en los pacientes y extender la esperanza de vida de los mismos. Asimismo, ME vítreas cargadas con el radioisótopo ³²P, ofrecen una alternativa a los tratamientos con ME de ⁹⁰Y, que actualmente se importan de Canadá y Australia a altos costos. En este trabajo se presentan las pruebas y cálculos preliminares de irradiación para obtener ³²P a partir del isótopo estable ³¹P en una matriz vítrea, utilizando para ello el reactor nuclear RA-6. Los cálculos se realizaron considerando la activación neutrónica del ³¹P en la caja de irradiación I del RA-6, la cual posee un flujo térmico integrado de aproximadamente 1,4 .10¹³cm⁻²s⁻¹ y uno epidérmico de 8 . 10¹¹cm⁻²s⁻¹. Para una composición vítrea tipo PASM (42P₂O₅-4SiO₂-10Al₂O₃-44MgO) el estudio de las tasas de reacción para la captura radiativa y posterior decaimiento indican que es suficiente con un tiempo de irradiación de 24 horas y uno de decaimiento de 72 horas. Las actividades y dosis por ME aplicadas a 1kg de tejido, con ME de 60μm de diámetro de ³²P en matriz PASM resultan en 73Bq/ME y 14,4μGy/ME. En comparación, las dosis de ME comerciales de ⁹⁰Y corresponden a 2,5μGy/ME para las ME de resina Sir-Spheres y a 175μGy/ME para las ME vítreas Therasphere. Luego, la estimación de la dosis administrada por estas ME se llevó a cabo utilizando el método multicompartimento en hígado. Por otro lado, se realizaron simulaciones Monte Carlo con la plataforma GATE, para evaluar la calidad de imagen obtenida a partir de los fotones de Bremsstrahlung del ³²P con diferentes parámetros de adquisición. A su vez, se simulo la adquisición de imágenes de ⁹⁹mTc, que fueron luego comparadas con imágenes adquiridas en el equipo SPECT/CT de INTECNUS, en un Fantoma antropomórco de hígado diseñado y fabricado, mediante impresión 3D.

Resumen en inglés

Hepatocellular carcinoma (HCC) is one of the main incidence and mortality factors among liver cancer, causing annually more than half a million deaths worldwide. Selective internal radiation therapy (SIRT) using pure β- emitting radioisotopes microspheres (MS) are used in palliative treatment of patients, extending their life expectancy. Likewise, vitreous MS loaded with the ³²P radioisotope, offer an alternative to ⁹⁰Y MS treatments, which are currently imported from Canada and Australia at high prices. In this project, preliminary irradiation tests and calculations are presented to obtain ³²P from the stable isotope ³¹P in a vitreous matrix, using the RA-6 nuclear reactor. Computation were carried out considering the neutron activation of ³¹P in the irradiation box I of the RA-6, which has an integrated thermal flux of approximately 1,4.10¹³cm⁻²s⁻¹ and an epithermal flux of 8 . 10¹¹cm⁻²s⁻¹. For a PASM-type vitreous composition (42P₂O₅-4SiO₂-10Al₂O₃-44MgO) the study of the reaction rates for neutronic capture and subsequent decay indicates that an irradiation time of 24 hours and a decay time of 72 hours is enough to achieve an acceptable activity of ³²P. The activities and doses per MS applied to 1kg of tissue, with 60μm diameter MS of ³²P in PASM matrix result in 73Bq/MS and 14.4μGy/MS. In comparison, the commercial MS doses for 90Y correspond to 2.5μGy/MS for Sir-Spheres (resin MS) and 175μGy/MS for Therasphere (vitreous MS). Then, the estimation of the dose administered by these ³²P MS was carried out using the multi-compartment method in liver. On the other hand, Monte Carlo simulations with the GATE platform were used to evaluate the image quality obtained from the Bremsstrahlung photons of ³²P applying different acquisition parameters. As well, ⁹⁹mTc imaging was simulated, comparing simulated images with the acquired ones, obtained by INTECNUS SPECT/CT equipment, using a anthropomorphic liver phantom, which was designed and manufactured with a 3D printing for this purpose, allowing this the validation of the simulation tool.

Tipo de objeto:Tesis (Proyecto Integrador Ingeniería Nuclear)
Palabras Clave:Irradiation; Irradiación; Phantoms; Neutron activation analysis; Análisis por activación neutrónica; [Hepatocellular carcinoma; Hepatocarcinoma; Fantoma]
Referencias:[1] Cardoso Cuneo, J., Prado, M., Vanzulli, S., Rivera Figueroa, E., Colombo, L., Parodi, L., et al. Proyecto para producción y estudio experimental de aplicación de microesferas sólidas de aluminosilicato de ytrio para radioembolizacion y porosas de sílice para quimioembolizacion. Revista de la Asociación Argentina de Biología y Medicina Nuclear, vol 5, 46-55, 05 2014. xvii, xviii, 10, 55, 59 [2] IAEA. Nuclear data services. https://www-nds.iaea.org/, Octubre 2020. xvii,xvii, 18, 21, 22, 25 [3] MatWeb. Material property data. http://www.matweb.com/, Septiembre 2020. xvii, 30, 31 [4] Directory, F. Plastics properties. https://www.filaments.directory/en/plastics, Septiembre 2020. xvii, 30, 31 [5] University, J. H. Imaging for surgery, therapy, and radiology. https://istar.jhu.edu/downloads/, Septiembre 2020. xvii, 31, 32 [6] Siewerdsen, J. H., Waese, A. M., Moseley, D. J., Richard, S., Jaray, D. A. Spektr: A computational tool for x-ray spectral analysis and imaging system optimization. Medical Physics, 31 (11), 3057-3067, Oct 2004. URL http://dx.doi.org/10.1118/1.1758350. xvii, 31, 32 [7] 5. CT X-Ray-Spectrum Characterization. Journal of the International Com- mission on Radiation Units and Measurements, 12 (1), 47-53, 04 2012. URL https://doi.org/10.1093/jicru/nds005. xvii, 31, 32 [8] Boone, J. M., Brink, J. A., Edyvean, S., Huda, W., Leitz, W., McCollough, C. H., et al. 5. ct x-ray-spectrum characterization. Journal of the ICRU, 12 (1), 47-53, Apr 2012. URL http://dx.doi.org/10.1093/jicru/nds005. xvii, 31, 32 [9] GE-Healthcare. Discovery nm/ct 670: System overview and safety manual for operators, 2010. xvii, 34 [10] Bastiaannet, R., Kappadath, S. C., Kunnen, B., Braat, A. J. A. T., Lam, M. G. E. H., de Jong, H. W. A. M. The physics of radioembolization. EJNMMI Physics, 5 (1), Nov 2018. URL http://dx.doi.org/10.1186/s40658-018-0221-z. 5, 15, 16, 17, 18, 51 [11] IAEA. Diagnostic radiopharmaceuticals. https://www.iaea.org/topics/diagnostic-radiopharmaceuticals, Noviembre 2020. 5 [12] Noguez Mendez, N. A., Quirino Barreda, C. T., Vega, A. F., Miranda Calderon, J. E., Urioste, C. G., Palomec, X. C., et al. Design and development of pharmaceutical microprocesses in the production of nanomedicine, pag. 669-697. Elsevier, 2017. URL http://dx.doi.org/10.1016/b978-0-323-47720-8.00023-7. 6 [13] Llamazares, A. H. V. R. Desarrollo de microesferas radioactivas vítreas para aplicaciones de terapia radiante interna selectiva a tumores malignos, tesis de maestria. Instituto Balseiro, Comisión Nacional de Energía Atómica y Universidad Nacional de Cuyo, Bariloche, Argentina, 2006. 6 [14] Figueroa, E. R. Desarrollo de microesferas cerámicas porosas para aplicaciones en quimioterapia interna selectiva a tumores malignos, tesis de maestría. Instituto Balseiro, Comisión Nacional de Energía Atómica y Universidad Nacional de Cuyo, Bariloche, Argentina, 2012. 6 [15] Zhang, D.-S. Effect of phosphorus-32 glass microspheres on human hepatocellular carcinoma in nude mice. World Journal of Gastroenterology, 10 (11), 1551, 2004. URL http://dx.doi.org/10.3748/wjg.v10.i11.1551. 6, 7 [16] Choi, J., Kang, J. O. Basics of particle therapy ii: relative biological effectiveness. Radiation Oncology Journal, 30 (1), 1, 2012. URL http://dx.doi.org/10.3857/ roj.2012.30.1.1. 7 [17] Stabin, M. G. Radiation protection and dosimetry: An introduction to health physics. tomo 1, pags. 100-110. Springer, 1990. 7 [18] Goh, A. S.-W., Chung, A. Y.-F., Lo, R. H.-G., Lau, T.-N., Yu, S. W.-K., Chng, M., et al. A novel approach to brachytherapy in hepatocellular carcinoma using a phosphorous32 (32p) brachytherapy delivery device|a rst-in-man study. In- ternational Journal of Radiation Oncology*Biology*Physics, 67 (3), 786-792, Mar 2007. URL http://dx.doi.org/10.1016/j.ijrobp.2006.09.011. 7, 8, 11, 66 [19] Parikh, S., Hyman, D. Hepatocellular cancer: A guide for the internist. The American Journal of Medicine, 120 (3), 194-202, Mar 2007. URL http://dx.doi.org/10.1016/j.amjmed.2006.11.020. 8 [20] WHO. Cancer. https://www.who.int/en/news-room/fact-sheets/detail/ cancer, Noviembre 2020. 8 [21] Sene, F. F., Martinelli, J. R., Okuno, E. Synthesis and characterization of phosphateglass microspheres for radiotherapy applications. Journal of Non-Crystalline Solids, 354 (42-44), 4887-4893, Nov 2008. URL http://dx.doi.org/10.1016/j.jnoncrysol.2008.04.041. 8, 10, 21, 37 [22] european association for the study of the liver. Easl clinical practice guidelines:Management of hepatocellular carcinoma. Journal of Hepatology, 69, 2018. 9 [23] Mahnken, A. H. Current status of transarterial radioembolization. World Journal of Radiology, 8 (5), 449, 2016. URL http://dx.doi.org/10.4329/wjr.v8.i5.449. 9 [24] Kawashita, M., Miyaji, F., Kokubo, T., Takaoka, G. H., Yamada, I., Suzuki, Y., et al. Surface structure and chemical durability of p+-implanted y2o3-al2o3-sio2 glass for radiotherapy of cancer. Journal of Non-Crystalline Solids, 255 (2-3), 140-148, Oct 1999. URL http://dx.doi.org/10.1016/S0022-3093(99)00377-4. 9, 10 [25] LNHB, C. E. A. Table de radionuclfleides. http://www.nucleide.org/DDEP_WG/ Introduction_2011.pdf, Noviembre 2020. 9 [26] L. Caldarola, e. a., U. Rosa. Preparation of 32-p labelled resin microspheres for radiation treatment of tumours by intra-arterial injection. tomo 55, pags. 169-174. 1964. 11 [27] Grady, E. D. Diseases of the colon and rectum. tomo 22, no.6, pags. 371-375. 1979. 11 [28] Bouvry, C., Palard, X., Edeline, J., Ardisson, V., Loyer, P., Garin, E., et al. Transarterial radioembolization (tare) agents beyond 90y-microspheres. BioMed Research International, 2018, 1{14, Dec 2018. URL http://dx.doi.org/10.1155/2018/1435302. 11, 17 [29] Wang, X.-M., Yin, Z.-Y., Yu, R.-X., Peng, Y.-Y., Liu, P.-G., Wu, G.-Y. Preventive effect of regional radiotherapy with phosphorus-32 glass microspheres in hepatocellular carcinoma recurrence after hepatectomy. World Journal of Gastroenterology, 14 (4), 518, 2008. URL http://dx.doi.org/10.3748/wjg.14.518. 11 [30] Liu, L. Clinical and experimental study on regional administration of phosphorus 32 glass microspheres in treating hepatic carcinoma. World Journal of Gastroen-terology, 5 (6), 492, 1999. URL http://dx.doi.org/10.3748/wjg.v5.i6.492.11, 66 [31] Cherry, S., Sorenson, J., Phelps, M. Physics in Nuclear Medicine. Elsevier Inc., 2012. 12, 13 [32] D'Asseler, Y. SPECT/CT and Image Quality, pags. 179-192. 2017. 14, 15 [33] Bushberg, J. T., Seibert, A. J., Leidholdt, E. M., Boone, J. M. The essential physics of medical imaging; 3rd ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2012. URL https://cds.cern.ch/record/1425946. 15 [34] PhD, S. C. K. Yttrium-90 microsphere therapy planning and dose calculations - presentation, 2011 Anual Meeting. 16, 17, 18, 66 [35] Giammarile, F., Bodei, L., Chiesa, C., Flux, G., Forrer, F., Kraeber-Bodere, F., et al. Eanm procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. European Journal of Nuclear Medicine and Molecular Imaging, 38 (7), 1393-1406, Apr 2011. URL http://dx.doi.org/10.1007/s00259-011-1812-2. 16, 19, 66 [36] Evans, R. D. The atomic nucleus. tomo 1, pags. 170-175. Tata McGraw-Hill Publishing Company LTD., 1955. 19, 20 [37] Knoll, G. E. Radiation detection and measurement. tomo 1, pags. 744{751. John Wiley and Sons, Inc., 2000. 20 [38] OECD-NEA. Janis. https://www.oecd-nea.org/janisweb/, Marzo 2021. 25 [39] Agostinelli, S., Allison, J., Amako, K., Apostolakis, J., Araujo, H., Arce, P., et al. Geant4|a simulation toolkit. Nuclear Instruments and Methods in Phy- sics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 506 (3), 250-303, Jul 2003. URL http://dx.doi.org/10.1016/ s0168-9002(03)01368-8. 26 [40] Jan, S., Santin, G., Strul, D., Staelens, S., Assie, K., Autret, D., et al. Gate: a simulation toolkit for pet and spect. Physics in Medicine and Biology, 49 (19), 4543-4561, Sep 2004. URL http://dx.doi.org/10.1088/0031-9155/49/19/ 007. 26 [41] Jan, S., Benoit, D., Becheva, E., Carlier, T., Cassol, F., Descourt, P., et al. Gate v6: a major enhancement of the gate simulation platform enabling modelling of fict and radiotherapy. Physics in Medicine and Biology, 56 (4), 881-901, Jan 2011. URL http://dx.doi.org/10.1088/0031-9155/56/4/001. 26 [42] Sarrut, D., Bardies, M., Boussion, N., Freud, N., Jan, S., Letang, J.-M., et al. A review of the use and potential of the gate monte carlo simulation code for radiation therapy and dosimetry applications. Medical Physics, 41 (6Part1), 064301, May 2014. URL http://dx.doi.org/10.1118/1.4871617. 26 [43] Allison, J., Amako, K., Apostolakis, J., Araujo, H., Arce Dubois, P., Asai, M., et al. Geant4 developments and applications. IEEE Transactions on Nuclear Science, 53 (1), 270-278, Feb 2006. URL http://dx.doi.org/10.1109/tns. 2006.869826. 26 [44] Allison, J., Amako, K., Apostolakis, J., Arce, P., Asai, M., Aso, T., et al. Recent developments in geant4. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 835, 186-225, Nov 2016. URL http://dx.doi.org/10.1016/j.nima.2016.06.125. 26 [45] Lidan, K., Starpelt, N. Internal and external bremsstrahlung accompanying the beta rays of p32. Physical Review, 97, 1955. 26, 35, 51 [46] Pirayesh, E., Amoui, M., Akhlaghpoor, S., Tolooee, S., Khorrami, M., PoorBeigi, H., et al. Technical considerations of phosphorous-32 bremsstrahlung spect imaging after radioembolization of hepatic tumors: A clinical assessment with a review of imaging parameters. Radiology Research and Practice, 2014, 1-7, 2014. URL http://dx.doi.org/10.1155/2014/407158. 27, 51, 66 [47] DeWerd, L. A., Lawless, M. Introduction to Phantoms of Medical and Health Physics, pag. 1-14. Springer New York, 2013. URL http://dx.doi.org/10.1007/978-1-4614-8304-5_1. 28, 29 [48] Leng, S., Yu, L., Vrieze, T., Kuhlmann, J., Chen, B., McCollough, C. H. Construction of realistic liver phantoms from patient images using 3d printer and its application in ct image quality assessment. En: C. Hoeschen, D. Kontos, T. G. Flohr (eds.) Medical Imaging 2015: Physics of Medical Imaging. SPIE, 2015. URL http://dx.doi.org/10.1117/12.2082121. 29 [49] Awad, R. H., Habash, S. A., Hansen, C. J. 3D Printing Methods, pag. 11-32. Elsevier, 2018. URL http://dx.doi.org/10.1016/B978-0-12-803917-5.00002-X. 30, 36 [50] NIST. Xcom. https://physics.nist.gov/PhysRefData/Xcom/html/xcom1. html, Septiembre 2020. 30 [51] Bryant, J., Drage, N., Richmond, S. Ct number denition. Radiation Physics and Chemistry, 81 (4), 358-361, Apr 2012. URL http://dx.doi.org/10.1016/j.radphyschem.2011.12.026. 31 [52] H. Q. Woodard, P., D. R. White, P. The composition of body tissues. The British Journal of Radiology, 1986. 32 [53] NIST. Composition of tissue, soft. https://physics.nist.gov/cgi-bin/Star/compos.pl?matno=261, Septiembre 2020. 32 [54] Kanematsu, N., Inaniwa, T., Nakao, M. Modeling of body tissues for monte carlo simulation of radiotherapy treatments planned with conventional x-ray ct systems. Physics in Medicine and Biology, 61 (13), 5037{5050, Jun 2016. URL http://dx.doi.org/10.1088/0031-9155/61/13/5037. 32 [55] May, C. Epoxy Resins: Chemistry and Technology, Second Edition,. CRC Press, 2018. URL https://books.google.com.ar/books?id=YlQPEAAAQBAJ. 33 [56] Ali Chamas, e. a., Hyunjin Moon. Degradation rates of plastics in the environment. ACS Sustainable Chamistry and Engineering, 2020. 34 [57] Wady, P., Wasilewski, A., Brock, L., Edge, R., Baidak, A., McBride, C., et al. Effect of ionising radiation on the mechanical and structural properties of 3d printed plastics. Additive Manufacturing, 31, 100907, Jan 2020. URL http://dx.doi.org/10.1016/j.addma.2019.100907. 35 [58] Uk atomic energy authority: Fispact-ii. https://fispact.ukaea.uk/, Abril 2021.38 [59] NIH. Imagej: Image processing and analysis in java. https://imagej.nih.gov/ij/, Abril 2021. 43 [60] Sirtex. About sir-spheres microspheres. https://www.sirtex.com/us/ clinicians/about-sir-spheres-microspheres/, Abril 2021. 59
Materias:Medicina > Medicina nuclear
Medicina > Radiofarmacia
Divisiones:Centro Integral de Medicina Nuclear y Radioterapia. Fundación INTECNUS
Código ID:1023
Depositado Por:Tamara Cárcamo
Depositado En:27 Abr 2022 15:39
Última Modificación:27 Abr 2022 15:39

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