Porini, Sabrina L. (2018) Evaluación de la biodistribución y dosis absorbidas en aplicaciones terapéuticas con 223"Ra en pacientes con cáncer de próstata. / Evaluation of biodistribution and absorbed dose in therapeutic application with 223"Ra in patients with prostate cancer. Maestría en Física Médica, Universidad Nacional de Cuyo, Instituto Balseiro.
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Resumen en español
El cáncer de próstata es una de las principales causas de muerte por cáncer entre los hombres en la Argentina y en el mundo. Esta enfermedad afecta principalmente a los hombres mayores de 65 años. Si es detectada en un estadio temprano las posibilidades de curación son altas pero si se detecta en un estadio avanzado, en donde el cáncer se ha diseminado al resto del cuerpo, se vuelve difícil combatirla. El Dicloruro de Radio-223 (223"RaCl_2) es un radiofármaco que se utiliza para tratar el cáncer de próstata en el estadio en el cual se ha propagado a los huesos formando metástasis. Las propiedades físicas y químicas del 223"Ra producen un efecto terapéutico sobre las metástasis oseas. Por su parte, el 223"Ra es principalmente un emisor de partículas alfa. Cuenta con una progenie radiactiva de seis hijas que decaen, emitiendo a su vez partículas alfa y beta, hasta llegar al 207Pb estable. El 223"Ra, gracias a su configuración electrónica externa, posee una alta anidad por los sitios metastásicos óseos. Una vez depositado sobre la superficie del hueso, este radionucleido y su progenie emiten radiación ionizante, que extermina principalmente a las células cancerosas. En Medicina Nuclear, es muy importante cuantificar la entrega de radiación al paciente, de modo de otorgarle el mejor beneficio con el menor detrimento posible. Por lo tanto, estudiar la dosimetría y la biodistribución de los radiofármacos en el cuerpo humano es esencial. En la presente tesis de maestría, se propuso realizar un estudio de biodistribución y dosimetría del radiofármaco marcado con 223"Ra, administrado a un paciente con cáncer de próstata con metástasis oseas. El estudio consistió en la adquisición de imágenes del paciente bajo tratamiento utilizando una cámara gamma. A partir de las imágenes obtenidas y de un método de calculo disimétrico llamado MIRD (Medical Internal Radiation Dose), comunmente usado en Medicina Nuclear [1, 2], se determino la dosis absorbida en distintas regiones de interés del cuerpo del paciente. El procedimiento para la adquisición de las imágenes de 223"Ra y su progenie se definió mediante un protocolo, el cual se baso en la adquisición de imágenes planares del paciente inyectado con el radiofármaco. Posteriormente, mediante un software específico se cuantificaron las imágenes adquiridas y se determino la actividad presente en regiones de interés del cuerpo del paciente. Finalmente, con los datos obtenidos se calculo la dosis absorbida en cada una de estas regiones siguiendo los lineamientos establecidos en el método de calculo MIRD. Simultáneamente, se realizaron simulaciones con un programa Monte Carlo, llamado ATE [3]. Este programa permite calcular en modo directo parámetros disimétricos como la energía depositada y la dosis absorbida, debido a la desintegración de isotopos radiactivos como el 223"Ra, en cada punto de un determinado medio. El objetivo principal de las simulaciones con GATE fue el de determinar un factor fundamental en dosimetría interna utilizado para el calculo de la dosis absorbida. Este factor se denomina comúnmente valor S y esta definido como la dosis media absorbida en una región blanco, por desintegración del isotopo radiactivo, en una región fuente. Por consiguiente, este valor es constante para la posición y el tamaño de una fuente y de un blanco y para las propiedades del radionucleido considerado. Las simulaciones realizadas con GATE consistieron en la reproducción virtual del decaimiento de una fuente de 223"Ra en el volumen de esferas de agua de diferentes dimensiones. Con los datos de la energía depositada en cada una de las esferas, obtenidos mediante el programa GATE, se calculo la dosis media absorbida por desintegración de 223"Ra, es decir el valor S de 223"Ra para cada una de las esferas simuladas. Con el propósito de validar los resultados obtenidos con el programa GATE para el parámetro S, se realizo una comparación de los valores S obtenidos con GATE con los obtenidos mediante el software OLINDA/EXM, de uso corriente en los servicios de Medicina Nuclear para estudios disimétricos [4]. La comparación evidencio una diferencia relativa, entre los valores S determinados con ambos programas, menor al 1,5%. También se propuso verificar el carácter constante del producto de cada valor S por la masa de su respectiva esfera. Por definicion el valor S es inversamente proporcional a la masa y directamente proporcional a un termino constante característico del radioisotopo. En este termino se encuentran definidas las energías de la radiación emitida por transición nuclear y la fracción de energía absorbida por el medio relativa al tipo de radiación emitida. El resultado del producto (S.m) resulto constante para todas las esferas. Siempre mediante las simulaciones con GATE se propuso verificar la energía emitida por desintegración de 223"Ra en fantomas esféricos de agua. El valor de esta energía, en todos los fantomas, fue aproximadamente 5,77 MeV por desintegración de 223"Ra. Este valor se aproxima a los valores de energía emitida mas probables encontrados, en literatura que van desde los 5,54 MeV hasta los 5,75 MeV por desintegración de 223"Ra [5]. Finalmente, mediante el programa GATE se simulo la desintegración de una fuente de 223"Ra y su progenie en un fantoma de agua virtual identifico al volumen de las regiones de interés evaluadas en las imágenes adquiridas del paciente inyectado con Dicloruro de Radio-223 en la primera parte de nuestros estudios. El objetivo de esta simulación fue calcular el valor de S del 223"Ra y su progenie. Una vez obtenido este valor se lo comparo con el valor de S calculado con el método de calculo MIRD. La diferencia relativa entre ambos valores S fue aproximadamente del 1%. Por otro lado, se evaluó la energía depositada por desintegración del 223"Ra y su progenie. El valor encontrado para esta energía fue aproximadamente 27,86 MeV. La diferencia relativa encontrada entre este valor obtenido con GATE y el valor publicado en otros estudios [6] fue aproximadamente 1,2%, lo cual se considera un buen resultado de la energía depositada simulada por el programa GATE. Consideramos importante seguir trabajando con las simulaciones mediante un programa como GATE. Este programa, además de calcular la energía depositada por una fuente radiactiva y la dosis absorbida en volúmenes simétricos como las esferas, también permite virtualizar partes del cuerpo humano a partir de la segmentación de órganos y tejidos en las imágenes tomográficas del paciente. Por lo tanto, mediante GATE sería posible calcular el valor S del 223"Ra y su progenie en los órganos y tejidos de interés del cuerpo de pacientes reales. Este valor es fundamental en el método MIRD para el calculo de la dosis absorbida. Las simulaciones Monte Carlo pueden resultar una herramienta de apoyo muy útil en Medicina Nuclear cuando se trabaja con radionucleidos terapéuticos como el 223"Ra, dado que para las simulaciones no se requiere la presencia del radiofármaco. Sabemos que el mismo, posee un elevado costo y su disponibilidad esta sujeta a la realización de cada tratamiento. También se podría emplear el programa GATE para simular fuentes con geometrías símiles a la de los sitios de mayor captación y retención de 223"Ra y su progenie. En el tejido oseo sería ideal poder determinar la energía depositada en los nichos trabeculares óseos en proximidades de las metástasis oseas. Por medio de estas simulaciones, se podría estimar la dosis absorbida particularmente por la médula ósea allá presente, que al ser un tejido de elevada radiosensibilidad, limita la cantidad de actividad que un paciente puede recibir.
Resumen en inglés
Prostate cancer is one of the leading causes of cancer deaths among men worldwide and in Argentina. This disease aects mainly men over 65 years old. If it is detected at an early stage, the possibilities of healing are high but if it is detected at an advanced stage, where the cancer has spread to the rest of the body, it becomes diffcult to ght against it. Radium-223 dichloride (223"RaCl_2) is a radiopharmaceutical that is being used to treat prostate cancer at the stage where it has spread to the bones, forming metastasis. The physical and chemical properties of 223"Ra produce a therapeutic effect on bone metastases. In one hand, 223"Ra is mainly an alpha emitter. It has a radioactive progeny of six daughters, that decay by emitting alpha and beta particles, to reach stable lead (207Pb). Due to its external electronic conguration, 223Ra, also has a high afinity for sites of bone metastasis. Once it has been deposited on the tumor site, 223"Ra and its progeny emits ionizing radiation that exterminates mainly carcinogenic cells. In Nuclear Medicine, it is very important to quantify the radiation delivered to patients, in order to give them the best benet out of the treatment with the least possible detriment. Therefore, it is essential to study the dosimetry and biodistribution of radiopharmaceuticals in the human body. In the present master's thesis, it has been proposed to carry out a biodistribution and dosimetry study of the radiopharmaceutical labeled with 223"Ra, which was administered to a patient with prostate cancer and with bone metastases. The study consisted in the acquisition of images of the patient under treatment using a gamma camera. Based on the images obtained and with a dosimetric calculation method called MIRD (Medical Internal Radiation Dose) [1, 2], commonly used in Nuclear Medicine, the absorbed dose was determined in different regions of interest of the patient's body. The procedure for the acquisition of images of 223"Ra and its progeny was dened through a protocol, which was based on the acquisition of planar images of the patient injected with the radiopharmaceutical. Subsequently, by employing an image quantication software the activity present at the regions of interest of the patient's body was determined. Finally, with the data obtained, the absorbed dose in each of these regions was calculated following the guidelines established in the MIRD calculational method. Simultaneously, simulations were carried out with a Monte Carlo program, called GATE [3]. This program allows the calculation in a direct mode of dosimetric parameters such as the energy deposited and the absorbed dose, at each point in a given medium, due to the disintegration of radioactive isotopes like 223"Ra. The main goal of the simulations with GATE was to determine a fundamental factor in internal dosimetry used for the calculation of the absorbed dose. This factor is commonly known as the S-value and is dened as the average absorbed dose in a target region, due to the disintegration of a radioactive isotope, in a source region. Therefore, this value is constant for the position and size of a source and a target regions and for the properties of the radionuclide being considered. The simulations with GATE consisted of virtual reproductions of a decaying source of 223"Ra inside the volume of water spheres of different dimensions. With the data of the energy deposited, per disintegration of 223Ra, in each of the spheres obtained through the GATE program the mean abosorbed dose was calculated, that is to say the S-value of 223"Ra for each of the spheres. In order to validate the results obtained with the GATE program for the S parameter, a comparison was made with those obtained by the software OLINDA/ EXM, commonly used in Nuclear Medicine services for dosimetric studies [4]. The comparison showed a relative difference between the S-values determined with both programs, less than 1,5%. It was also proposed to verify the constant nature of the product of each S-value by the mass of its respective sphere. By denition, the S-value is inversely proportional to the mass and directly proportional to a constant term characteristic of the radioisotope. In this term, the emitted radiation energies per nuclear transition are dened as well as the energy absorbed fraction by the medium relative to each type of radiation emitted. The result for the product (S.m) was constant for all spheres. Always through GATE simulations it was proposed to verify the energy emitted by disintegration of 223"Ra in spherical water phantoms. This energy value, in all of the phantoms, was approximately 5,77 MeV per disintegration of 223"Ra. This value approximates the most likely values of emitted energy per desintegration of 223"Ra found in literature. These values lies within a range that goes from 5,54 MeV up to 5,75 MeV [5]. Finally, by means of the GATE program, it was simulated the disintegration a of source of 223"Ra and its progeny in a virtual water phantom identical to the volume of the regions of interest evaluated in the images acquired of the patient, who was injected with Radium-223 Dichloride. The goal of this simulation was to calculate the S-value of 223"Ra and its progeny. Once this value was obtained it was compared with the S-value calculated by the MIRD calculational method. The relative dierence between both the S-values was approximately 1%. On the other hand, the energy deposited by desintegration of 223"Ra and its progeny was assessed. The value found for this energy, was approximately 27,86 MeV. The relative difference found between this value obtained with GATE and the value published in other studies [6] it was approximately 1,2%, which was considered a good result for the energy deposited by 223"Ra, simulated by the GATE program. We consider that it is important to continue working on simulations through programs like GATE. This program, besides calculating the energy deposited by a radioactive source and the absorbed dose in symmetrical volumes such as spheres, also allows to virtualise parts of the human body from the segmentation of organs and tissues in tomographic images of the patient. Therefore, through GATE program it would be possible to calculate the S-value of 223"Ra and its progeny, in organs and tissues of interest. This value is fundamental in the MIRD method for calculating of the dose absorbed. Monte Carlo simulations can be a very useful and supporting tool in Nuclear Medicine, when working with therapeutic radionuclides such as 223"Ra. Mainly because its presence is not required for the simulations and because we know that it has a high cost and its availability is subject to the completion of each treatment. In particular, the GATE program could also be used to simulate sources with geometries similar to that of the sites with the highest uptake and retention of 223"Ra and its progeny. In the bone tissue it would be important to determine the energy deposited in the trabecular bone niches in proximities of bone metastases. In this way, it could be assessed the absorbed dose in the bone marrow, which is present therein and that has a high radiosensitivity, which limits the amount of activity that a patient can receive.
| Tipo de objeto: | Tesis (Maestría en Física Médica) |
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| Palabras Clave: | Prostate; Próstata, Neoplasms; Cáncer; Dosimitry; Dosimetría |
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| Materias: | Medicina > Medicina nuclear Medicina > Física médica |
| Divisiones: | FUESMEN |
| Código ID: | 775 |
| Depositado Por: | Tamara Cárcamo |
| Depositado En: | 17 Feb 2021 09:10 |
| Última Modificación: | 17 Feb 2021 09:44 |
Personal del repositorio solamente: página de control del documento
