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Transarterial radioembolization (TARE) is a locoregional radiopharmaceutical therapy based on the delivery of radioactive 90Y microspheres to liver tumors. The importance of personalized dosimetry to make TARE safer and more effective has been demonstrated in recent clinical studies, stressing the need for quantification of the dose-response relationship to ultimately optimize the administered activity before treatment and image it after treatment. 90Y dosimetric studies are challenging because of the lack of accurate and precise methods but are best realized with PET combined with Monte Carlo simulations and other image modalities to calculate a segmental dose distribution. The aim of this study was to assess the suitability of imaging 90Y PET patients with the total-body PET/CT uEXPLORER and to investigate possible improvements in TARE 90Y PET-based dosimetry. The uEXPLORER is the first commercially available ultra-high-resolution (171 cps/kBq) total-body digital PET/CT device with a 194-cm axial PET field of view that enables the whole body to be scanned at a single bed position. Methods: Two PET/CT scanners were evaluated in this study: the Biograph mCT and the total-body uEXPLORER. Images of a National Electrical Manufacturers Association (NEMA) image-quality phantom and 2 patients were reconstructed using our standard clinical oncology protocol. A late portal phase contrast-enhanced CT scan was used to contour the liver segments and create corresponding volumes of interest. To calculate the absorbed dose, Monte Carlo simulations were performed using Geant4 Application for Tomographic Emission (GATE). The absorbed dose and dose-volume histograms were calculated for all 6 spheres (diameters ranging from 10 to 37 mm) of the NEMA phantom, the liver segments, and the entire liver. Differences between the phantom doses and an analytic ground truth were quantified through the root mean squared error. Results: The uEXPLORER showed a higher signal-to-noise ratio at 10

[ES] El objetivo del presente Trabajo Final de Máster (TFM) es realizar un estudio dosimétrico de un tratamiento de braquiterapia hepática que emplea microesferas de Y-90 mediante simulación empleando el método de Monte Carlo. Si bien, un tratamiento de braquiterapia consiste en la introducción de la fuente en el interior del tumor, en concreto, para los carcinomas hepáticos, se emplea la radioembolización que consiste en la introducción de dichas semillas mediante la arteria hepática. Por ello, es importante conocer la dosis exacta que recibe el hígado, así como otros órganos colindantes que se pueden ver vascularmente afectados como es el caso del pulmón o el tracto gastrointestinal. Para ello, se emplea el modelo anatómico 3D distribuido recientemente por la Comisión Internacional de Protección Radiológica (ICRP) conocido como Fantoma Computacional de Referencia de Tipo de Malla (MRCP). Una vez segmentado el maniquí, se simula el tratamiento con el método de Monte Carlo, haciendo uso del código MCNP, introduciendo una fuente de Y-90 en el interior del hígado, así como todas las especificaciones de la física del transporte de fotones y electrones necesaria para la simulación. Como resultado, se obtiene la dosis que recibe el tumor del hígado, así como cada órgano colindante en un tratamiento de estas características. Se comprueba, además, que las dosis recibidas son seguras y se ajustan con los resultados empíricos. Con ello se demuestra que este método de simulación puede resultar adecuado para planificar tratamientos de braquiterapia obteniendo resultados fiables en un tiempo de computación asequible., [EN] The objective of this Master's Final Project (TFM) is to carry out a dosimetric study of a liver brachytherapy treatment that uses Y-90 microspheres by simulation using the Monte Carlo method. Although, a brachytherapy treatment consists of the introduction of the source into the tumor, in particular, for liver carcinomas, radioembolization is used, which consists of the introduction of these seeds through the hepatic artery. Therefore, it is important to know the exact dose received by the liver, as well as other adjoining organs that may be vascularly affected as is the case of the lung or the gastrointestinal tract. To do this, the 3D anatomical model recently distributed by the International Commission on Radiological Protection (ICRP) known as Mesh Type Reference Computational Fantoma (MRCP) is used. Once the mannequin is segmented, the treatment is simulated with the Monte Carlo method, making use of the MCNP code, introducing a Y-90 source inside the liver, as well as all the specifications of the physics of photon and electron transport necessary for the simulation. As a result, the dose received by the liver tumor is obtained, as well as each adjoining organ in a treatment of these characteristics. It is also verified that the doses received are safe and are adjusted with the empirical results. This demonstrates that this simulation method can be suitable for planning brachytherapy treatments obtaining reliable results in an affordable computer time.

[ES] El objetivo del presente Trabajo Final de Máster (TFM) es realizar un estudio dosimétrico de un tratamiento de braquiterapia hepática que emplea microesferas de Y-90 mediante simulación empleando el método de Monte Carlo. Si bien, un tratamiento de braquiterapia consiste en la introducción de la fuente en el interior del tumor, en concreto, para los carcinomas hepáticos, se emplea la radioembolización que consiste en la introducción de dichas semillas mediante la arteria hepática. Por ello, es importante conocer la dosis exacta que recibe el hígado, así como otros órganos colindantes que se pueden ver vascularmente afectados como es el caso del pulmón o el tracto gastrointestinal. Para ello, se emplea el modelo anatómico 3D distribuido recientemente por la Comisión Internacional de Protección Radiológica (ICRP) conocido como Fantoma Computacional de Referencia de Tipo de Malla (MRCP). Una vez segmentado el maniquí, se simula el tratamiento con el método de Monte Carlo, haciendo uso del código MCNP, introduciendo una fuente de Y-90 en el interior del hígado, así como todas las especificaciones de la física del transporte de fotones y electrones necesaria para la simulación. Como resultado, se obtiene la dosis que recibe el tumor del hígado, así como cada órgano colindante en un tratamiento de estas características. Se comprueba, además, que las dosis recibidas son seguras y se ajustan con los resultados empíricos. Con ello se demuestra que este método de simulación puede resultar adecuado para planificar tratamientos de braquiterapia obteniendo resultados fiables en un tiempo de computación asequible., [EN] The objective of this Master's Final Project (TFM) is to carry out a dosimetric study of a liver brachytherapy treatment that uses Y-90 microspheres by simulation using the Monte Carlo method. Although, a brachytherapy treatment consists of the introduction of the source into the tumor, in particular, for liver carcinomas, radioembolization is used, which consists of the introduction of these seeds through the hepatic artery. Therefore, it is important to know the exact dose received by the liver, as well as other adjoining organs that may be vascularly affected as is the case of the lung or the gastrointestinal tract. To do this, the 3D anatomical model recently distributed by the International Commission on Radiological Protection (ICRP) known as Mesh Type Reference Computational Fantoma (MRCP) is used. Once the mannequin is segmented, the treatment is simulated with the Monte Carlo method, making use of the MCNP code, introducing a Y-90 source inside the liver, as well as all the specifications of the physics of photon and electron transport necessary for the simulation. As a result, the dose received by the liver tumor is obtained, as well as each adjoining organ in a treatment of these characteristics. It is also verified that the doses received are safe and are adjusted with the empirical results. This demonstrates that this simulation method can be suitable for planning brachytherapy treatments obtaining reliable results in an affordable computer time.

[ES] El objetivo del presente Trabajo Final de Máster (TFM) es realizar un estudio dosimétrico de un tratamiento de braquiterapia hepática que emplea microesferas de Y-90 mediante simulación empleando el método de Monte Carlo. Si bien, un tratamiento de braquiterapia consiste en la introducción de la fuente en el interior del tumor, en concreto, para los carcinomas hepáticos, se emplea la radioembolización que consiste en la introducción de dichas semillas mediante la arteria hepática. Por ello, es importante conocer la dosis exacta que recibe el hígado, así como otros órganos colindantes que se pueden ver vascularmente afectados como es el caso del pulmón o el tracto gastrointestinal. Para ello, se emplea el modelo anatómico 3D distribuido recientemente por la Comisión Internacional de Protección Radiológica (ICRP) conocido como Fantoma Computacional de Referencia de Tipo de Malla (MRCP). Una vez segmentado el maniquí, se simula el tratamiento con el método de Monte Carlo, haciendo uso del código MCNP, introduciendo una fuente de Y-90 en el interior del hígado, así como todas las especificaciones de la física del transporte de fotones y electrones necesaria para la simulación. Como resultado, se obtiene la dosis que recibe el tumor del hígado, así como cada órgano colindante en un tratamiento de estas características. Se comprueba, además, que las dosis recibidas son seguras y se ajustan con los resultados empíricos. Con ello se demuestra que este método de simulación puede resultar adecuado para planificar tratamientos de braquiterapia obteniendo resultados fiables en un tiempo de computación asequible., [EN] The objective of this Master's Final Project (TFM) is to carry out a dosimetric study of a liver brachytherapy treatment that uses Y-90 microspheres by simulation using the Monte Carlo method. Although, a brachytherapy treatment consists of the introduction of the source into the tumor, in particular, for liver carcinomas, radioembolization is used, which consists of the introduction of these seeds through the hepatic artery. Therefore, it is important to know the exact dose received by the liver, as well as other adjoining organs that may be vascularly affected as is the case of the lung or the gastrointestinal tract. To do this, the 3D anatomical model recently distributed by the International Commission on Radiological Protection (ICRP) known as Mesh Type Reference Computational Fantoma (MRCP) is used. Once the mannequin is segmented, the treatment is simulated with the Monte Carlo method, making use of the MCNP code, introducing a Y-90 source inside the liver, as well as all the specifications of the physics of photon and electron transport necessary for the simulation. As a result, the dose received by the liver tumor is obtained, as well as each adjoining organ in a treatment of these characteristics. It is also verified that the doses received are safe and are adjusted with the empirical results. This demonstrates that this simulation method can be suitable for planning brachytherapy treatments obtaining reliable results in an affordable computer time.

[ES] El objetivo del presente Trabajo Final de Máster (TFM) es realizar un estudio dosimétrico de un tratamiento de braquiterapia hepática que emplea microesferas de Y-90 mediante simulación empleando el método de Monte Carlo. Si bien, un tratamiento de braquiterapia consiste en la introducción de la fuente en el interior del tumor, en concreto, para los carcinomas hepáticos, se emplea la radioembolización que consiste en la introducción de dichas semillas mediante la arteria hepática. Por ello, es importante conocer la dosis exacta que recibe el hígado, así como otros órganos colindantes que se pueden ver vascularmente afectados como es el caso del pulmón o el tracto gastrointestinal. Para ello, se emplea el modelo anatómico 3D distribuido recientemente por la Comisión Internacional de Protección Radiológica (ICRP) conocido como Fantoma Computacional de Referencia de Tipo de Malla (MRCP). Una vez segmentado el maniquí, se simula el tratamiento con el método de Monte Carlo, haciendo uso del código MCNP, introduciendo una fuente de Y-90 en el interior del hígado, así como todas las especificaciones de la física del transporte de fotones y electrones necesaria para la simulación. Como resultado, se obtiene la dosis que recibe el tumor del hígado, así como cada órgano colindante en un tratamiento de estas características. Se comprueba, además, que las dosis recibidas son seguras y se ajustan con los resultados empíricos. Con ello se demuestra que este método de simulación puede resultar adecuado para planificar tratamientos de braquiterapia obteniendo resultados fiables en un tiempo de computación asequible., [EN] The objective of this Master's Final Project (TFM) is to carry out a dosimetric study of a liver brachytherapy treatment that uses Y-90 microspheres by simulation using the Monte Carlo method. Although, a brachytherapy treatment consists of the introduction of the source into the tumor, in particular, for liver carcinomas, radioembolization is used, which consists of the introduction of these seeds through the hepatic artery. Therefore, it is important to know the exact dose received by the liver, as well as other adjoining organs that may be vascularly affected as is the case of the lung or the gastrointestinal tract. To do this, the 3D anatomical model recently distributed by the International Commission on Radiological Protection (ICRP) known as Mesh Type Reference Computational Fantoma (MRCP) is used. Once the mannequin is segmented, the treatment is simulated with the Monte Carlo method, making use of the MCNP code, introducing a Y-90 source inside the liver, as well as all the specifications of the physics of photon and electron transport necessary for the simulation. As a result, the dose received by the liver tumor is obtained, as well as each adjoining organ in a treatment of these characteristics. It is also verified that the doses received are safe and are adjusted with the empirical results. This demonstrates that this simulation method can be suitable for planning brachytherapy treatments obtaining reliable results in an affordable computer time.

Biologically stable 90Y-labelled albumin microspheres (AMS) were developed by optimizing the process of their preparation. Three formulations of 90Y-AMS were initially prepared with high radiolabelling yield but depending on the step when the radionuclide 90Y and DTPA chelator were added, radiolabelled microspheres with different in vitro and in vivo stability were obtained. DTPA was proved as a useful chelating agent that tightly links radionuclide 90Y to albumin. Also, AMS radiolabelled via DTPA during preparation and before microspheres stabilization, showed significant in vitro and in vivo stability ready for the potential use in selective internal radiation therapy. © 2019 Elsevier Ltd

Biologically stable 90Y-labelled albumin microspheres (AMS) were developed by optimizing the process of their preparation. Three formulations of 90Y-AMS were initially prepared with high radiolabelling yield but depending on the step when the radionuclide 90Y and DTPA chelator were added, radiolabelled microspheres with different in vitro and in vivo stability were obtained. DTPA was proved as a useful chelating agent that tightly links radionuclide 90Y to albumin. Also, AMS radiolabelled via DTPA during preparation and before microspheres stabilization, showed significant in vitro and in vivo stability ready for the potential use in selective internal radiation therapy. © 2019 Elsevier Ltd

Radioembolization of liver tumors using yttrium-90 (Y-90) labeled microspheres is a proven method of treatment. The primary decay mode of Y-90 is beta-minus decay. The electrons produced during decay deliver a cytotoxic radiation dose in a localized volume. The radiation dose is sufficient to kill tumor cells yet spare the normal liver. The Y-90 microspheres are delivered via a catheter that has been placed in an artery that supplies blood to the tumor. Microspheres are injected and the blood distributes the microspheres. The current practice involves two separate procedures. The first procedure is an assessment of the vasculature of the liver and tumor. This assessment is performed with radiolabeled macro-aggregated albumin particles (Tc-99m MAA). The Tc-99m MAA is injected via a catheter placed in the same location that will be used for the delivery of Y-90 microspheres. The distribution of the Tc-99m MAA particles is imaged using a gamma camera. This data is used to predict the microsphere distribution and subsequent dose to the tumor, normal liver, lungs and other organs. The data may be used to adjust the Y-90 activity and to perform crude pre-treatment dosimetry. Accurate pre-treatment dosimetry is largely absent. This study was performed to create a positron-emitting surrogate microsphere that was close in size and shape to the Y-90 microspheres. Positron emission tomography (PET) is superior to SPECT for activity quantification. Fluorine-18 (F-18) was chosen for initial experiments. There were two aims of the research: Aim 1: To develop surrogate PET microsphere. This included radiolabeling, stability testing in vitro and stability testing in an animal. Aim 2: To develop a computational technique to perform dosimetry with the surrogate microsphere. PET images of the surrogate radionuclide were imported into a Monte Carlo program. PET images were used to simulate the distribution of the Y-90 microspheres. The output of the simulation w

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe3O4-Naked (80 +/- 5 nm) and polyethylene glycol 600 diacid functionalized Fe3O4 (Fe3O4-PEG600) MNPs (46 +/- 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe3O4-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of Y-90-MNPs were compared. Both types of MNPs were Y-90-labeled in reproducible high yield ( GT 97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for Y-90-Fe3O4-Naked MNPs and 19.61%ID/g for Y-90-Fe3O4-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of Y-90-Fe3O4-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for Y-90-Fe3O4-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as Y-90-Fe3O4-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 126-134, 2015.

Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe3O4-Naked (80 +/- 5 nm) and polyethylene glycol 600 diacid functionalized Fe3O4 (Fe3O4-PEG600) MNPs (46 +/- 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe3O4-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of Y-90-MNPs were compared. Both types of MNPs were Y-90-labeled in reproducible high yield ( GT 97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for Y-90-Fe3O4-Naked MNPs and 19.61%ID/g for Y-90-Fe3O4-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of Y-90-Fe3O4-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for Y-90-Fe3O4-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as Y-90-Fe3O4-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy. (c) 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 126-134, 2015.

Purpose: Positron emission tomography (PET) with Zr-89-britumomab tiuxetan can be used to monitor biodistribution of Y-90-ibritumomab tiuxetan as shown in mice. The aim of this study was to assess biodistribution and radiation dosimetry of 90Y-ibritumomab tiuxetan in humans on the basis of Zr-89-ibritumomab tiuxetan imaging, to evaluate whether co-injection of a therapeutic amount of Y-90-ibritumomab tiuxetan influences biodistribution of Zr-89-ibritumomabtiuxetan and whether pre-therapy scout scans with Zr-89-ibritumomab tiuxetan can be used to predict biodistribution of Y-90-ibritumomab tiuxetan and the dose-limiting organ during therapy. Methods: Seven patients with relapsed B-cell non-Hodgkin's lymphoma scheduled for autologous stem cell transplantation underwent PET scans at 1, 72 and 144 h after injection of similar to 70 MBq Zr-89-ibritumomab tiuxetan and again 2 weeks later after co-injection of 15 MBq/kg or 30 MBq/kg Y-90-britumomab tiuxetan. Volumes of interest were drawn over liver, kidneys, lungs, spleen and tumours. Ibritumomab tiuxetan organ absorbed doses were calculated using OLINDA. Red marrow dosimetry was based on blood samples. Absorbed doses to tumours were calculated using exponential fits to the measured data. Results: The highest Y-90 absorbed dose was observed in liver (3.2 +/- 1.8 mGy/MBq) and spleen (2.9 +/- 0.7 mGy/MBq) followed by kidneys and lungs. The red marrow dose was 0.52 +/- 0.04 mGy/MBq, and the effective dose was 0.87 +/- 0.14 mSv/MBq. Tumour absorbed doses ranged from 8.6 to 28.6 mGy/MBq. Correlation between predicted pre-therapy and therapy organ absorbed doses as based on Zr-89-ibritumomab tiuxetan images was high (Pearson correlation coefficient r=0.97). No significant difference between pre-therapy and therapy tumour absorbed doses was found, but correlation was lower (r=0.75). Conclusion: Biodistribution of Zr-89-ibritumomab tiuxetan is not influenced by simultaneous therapy with Y-90-ibritumomab tiuxetan, and Zr-89-ibritu

Introduction: The aim of this study was to find out if Y-90 could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if Y-90-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases. Methods: The preparing of Y-90-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistrbution study in health male Wistar rats. In vitro stability of the complexes was tested too. Results: Y-90-DMSA could be prepared in high yields ( GT 95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that Y-90-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for Y-90-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible. Conclusions: Y-90 complexes could be made with ease with DMSA. Y-90-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.

Introduction: The aim of this study was to find out if Y-90 could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if Y-90-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases. Methods: The preparing of Y-90-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistrbution study in health male Wistar rats. In vitro stability of the complexes was tested too. Results: Y-90-DMSA could be prepared in high yields ( GT 95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that Y-90-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for Y-90-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible. Conclusions: Y-90 complexes could be made with ease with DMSA. Y-90-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.