Biokinetics, radiopharmacokinetics and estimation of the absorbed dose in healthy organs due to Technetium-99m transported in the core and on the surface of reconstituted high-density lipoprotein nanoparticles.

The development of rHDL-radionuclide theragnostic systems requires evaluation of the absorbed doses that would be produced in healthy tissues and organs at risk. Technetium-99m is the most widely used radionuclide for diagnostic imaging, therefore, the design of theragnostic reconstituted high density-lipoprotein (rHDL) nanosystems labeled with Technetium-99m offers multiple possibilities. OBJECTIVE: To determine the biokinetics, radiopharmacokinetics and estimate the absorbed doses induced in healthy organs by Technetium-99m transported in the core and on the surface of rHDL. METHODS: Biokinetic and radiopharmacokinetic models of rHDL/[99mTc]Tc-HYNIC-DA (Technetium-99m in the core) and [99mTc]Tc-HYNIC-rHDL (Technetium-99m on the surface) were calculated from their ex vivo biodistribution in healthy mice. Absorbed doses were estimated by the MIRD formalism using OLINDA/EXM and LMFIT softwares. RESULTS: rHDL/[99mTc]Tc-HYNIC-DA and [99mTc]Tc-HYNIC-rHDL show instantaneous absorption in kidney, lung, heart and pancreas, with slower absorption in spleen. rHDL/[99mTc]Tc-HYNIC-DA is absorbed more slowly in the intestine, while [99mTc]Tc-HYNIC-rHDL is absorbed more slowly in the liver. The main target organ for rHDL/[99mTc]Tc-HYNIC-DA, which is hydrophobic in nature, is the liver, whereas the kidney is for the more hydrophilic [99mTc]Tc-HYNIC-rHDL. Assuming that 925 MBq (25 mCi) of Technetium-99m, carried in the core or on the surface of rHDL, are administered, the maximum tolerated doses for the organs of greatest accumulation are not exceeded. CONCLUSION: Theragnostic systems based on 99mTc-labeled rHDL are safe from the dosimetric point of view. The dose estimates obtained can be used to adjust the 99mTc-activity to be administered in future clinical trials.

Comparison of Whole-Body Dosimetry Measurements in 131I Therapy Using Ceiling-Mounted Geiger-Müller Detectors and γ-Camera Scans: An Agreement Analysis.

Background: In 131I therapies internal dosimetry is crucial for determining the mean absorbed dose to organs at risk, particularly the bone marrow, which has a dose constraint of 2 Gy. Traditionally, multicompartmental models have been used for bone marrow dosimetry, necessitating whole-body absorbed-dose assessments. However, noninvasive techniques, such as γ-camera scans or ceiling-mounted Geiger-Müller (GM) counters, can estimate the aforementioned. This study was aimed to evaluate the agreement between whole-body mean absorbed dose using γ-camera scans and ceiling-mounted GM in patients with thyroid carcinoma undergoing 131I therapy. Methods: This study included 31 patients with thyroid cancer who were treated with 131I. The whole-body time-integrated activity (TIA) and mean absorbed dose were estimated using the elimination curves obtained with γ-camera scans and ceiling-mounted GM. In addition, statistical analysis was performed on the data to determine the Coefficient Correlation Coefficient and the Bland-Altman limits of agreement for both parameters, as well as for the elimination curves' effective half-life. Results: The study revealed correlations of 0.562 and 0.586 between whole-body TIA and mean absorbed dose, respectively. The Bland-Altman limits of agreement were found to be below -3.75% and within 12.75% of the bone marrow dose constraint of 2 Gy. The nonparametric evaluation revealed that whole-body TIA and mean absorbed dose medians from GM were lower than those from γ-camera scans (p < 0.001). Effective half-life estimation mean was significantly lower in the GM than in the γ-camera of 13 and 23 h. Conclusions: Although GM calculates the whole-body absorbed dose with margins of error within clinical acceptance, underestimation of the effective half-life makes it an unacceptable substitute method for γ-cameras in clinical practice. Further research should be conducted to evaluate single-point GM measurement substitutions in time-activity curves.

Attributable patient risk in nuclear medicine procedures and establishment of diagnostic reference levels.

The assessment of risk related to medical exposures as a justification tool to assist decision-making of the medical team is not available in clinical routine. The determination of diagnostic reference levels (DRLs) for nuclear medicine (NM) procedures has been proposed as an optimization tool, but this tool has still been aimed at a standard adult individual. It is known that the activity administered, and the consequent absorbed doses in critical organs, represents the risk of a procedure being cancer induction the greatest concern, especially for young patients. Thus, the adjustment of administered activity and procedure risk to promote risk-benefit assessment is a promising tool for routine clinical use. This work aims to present a tool for determining DRLs in the administered activity related to the patient's characteristics-age group, sex, and body mass index (BMI), in order to assist the medical decision regarding the risk-benefit ratio. Thus, it is possible to assess the risk of carcinogenesis in groups of patients, considering absorbed doses in organs, cancer incidence, and mortality rates in our country. NIREA is an IT tool developed in PHP language for web environment as a friendly software. It allows the establishment of DRL and risk of cancer induced by radiation assessment through the estimation of absorbed doses in specific organs and based on the risk methodology of BEIR VII. The absorbed and effective doses were estimated based on the dose conversion factors of the radiopharmaceuticals published by the International Commission on Radiological Protection adjusted for the patient groups. Based on data from 2256 patients who underwent diagnostic procedures at National Cancer Institute between 2017 and 2019, the program was used, resulting in important information for conducting the clinical routine extracted as DRL, absorbed doses, and risk assessments, considering patient-specific data such as age, sex, and BMI. The methodology developed in this work allows NM services to keep their data available and updated regarding local DRLs, in addition to allowing the nuclear physician to know the risk of each procedure performed, extracted by individual characteristics of the patient. The affirmative is significant because the data could be used by the regulatory body of practices with ionizing radiation in Brazil to establish a reference level in Activity that has not yet existed in the country.

Comparison between 177Lu-iPSMA and 225Ac-iPSMA dosimetry at a cellular level in an animal bone metastasis model.

The recent use of prostate-specific membrane antigen as a biological target have improved the theragnostic approach to prostate and other types of cancer. Radiopharmaceuticals based on PSMA inhibitors radiolabeled with beta emitters as Lutetium-177 have demonstrated remarkable efficacy and safety, however, their clinical evaluation have also shown that therapeutic response of bone located metastases is poorer than that presented by soft tissue lesions. These observations conducted to the development and study at different levels of PSMA-targeting alpha-particle therapy exhibiting effective and promising antitumor activity. However, some aspects of the use of alpha emitters such as cellular dosimetry should be considered before applying them safely. The aim of the present work was to compare and calculate the absorbed dose of 177Lu-iPSMA and 225Ac-iPSMA using an animal bone metastasis model and experimental data obtained from cellular fractionation. The number of disintegrations and the dose factors for the theragnostic iPSMA pair, molecule that can be radiolabeled with 177Lu or 225Ac, were determined based on MIRD methodology, and used to calculate the absorbed dose to cell nucleus. A five times difference between 225Ac-iPSMA and 177Lu-iPSMA average dose rate to the tumor was calculated, being 2.3 ± 0.037 for the first and 0.5 ± 0.018 Gy for the second, both for each activity unit (MBq) administered.

Scan factors and practices associated with radiation doses for chest CT: current Brazilian scenario.

The main purpose of this study was to compare the parameters of computed tomography (CT) and the corresponding patient doses undergoing chest CT scan examinations in different regions of Brazil, providing the current scenario of how these procedures are being carried out in the country as well as the patient dose distribution. Thirty institutions, across 17 states and the Federal District, participated in the survey. The evaluation included 30 multislice CTs of seven different models, manufactured by General Electric (GE) Healthcare. For each institution, data from 10 adult chest CT examinations, performed without contrast, were collected remotely. The analysis of the results showed a significant difference of the CTDIvolvalues, ranging from 1.1 mGy to 46.6 mGy in seven institutions. The mean value of CTDIvolwas higher than values found in the literature and the UK Reference Levels. It was also observed that, regardless of the region of the country, for the same CT model, different scanning parameters were used, which resulted in CTDIvolup to 5 times higher in some institutions. Repetitions of CT acquisitions and scouts with radiation field dimensions larger than the region of interest were found in 25% of chest examinations, resulting in higher absorbed doses. The results of this work show a mapping of the chest CT procedures, which enables the establishment of strategic plans for the country. In addition, each institution will be able to implement an appropriate optimization program and establish institutional reference levels.

Determination of the absorbed dose to water for medium-energy x-ray beams using Fricke dosimetry.

PURPOSE: For x-ray beams in the low and medium energy range, reference dosimetry is established in terms of air kerma. Fricke dosimetry has shown great potential in the absolute measurements of the absorbed dose to water for high-energy ranges. Therefore, the main purpose of this work was to compare the absorbed dose to water for medium-energy x-ray beams obtained through Fricke dosimetry with that obtained from the air kerma rate. METHODS: To determine the absorbed dose to water using Fricke dosimetry, the polyethylene bags methodology was chosen. Fricke solution was irradiated at four different beam qualities. The absorbed dose to water values obtained using Fricke dosimetry were compared to those obtained using the standard protocol, using the Z-score. RESULTS: Values of the Z-score were <2 for all measurements of absorbed dose to water, which means that the values obtained using Fricke dosimetry are equivalent to those obtained using the reference protocol. The combined standard uncertainty for the absorbed dose to water obtained by Fricke dosimetry was lower than that obtained with the ionization chamber. CONCLUSIONS: Chemical dosimetry using a standard FeSO4 solution has been demonstrated to be a potential option as a standard for the quantity absorbed dose to water for medium kV x-ray qualities.

Doses in eye lens, thyroid, salivary glands, mammary glands, and gonads, due to radiation scattered in dental orthopantomography.

In the aim to support treatments and diagnostics in Dentistry the most common radiographies are the periapical radiography and the dental panoramic. In the dental panoramic the X-ray beam is addressed into a large zone of the face obtaining the image of the upper and lower jaw. In this procedure part of the X-rays are scattered reaching some other parts of the patient body. In this work the absorbed dose in the eye lens, thyroid, salivary glands, mammary glands, and gonads, was measured in patients undergoing a dental orthopantomography. Measurements were carried out with thermolmuminiscent dosimeters. With the absorbed doses the Effective dose were calculated. The highest dose was obtained in the salivary glands (30.4 µSv) and the lowest dose was obtained in thyroid (3.8 µSv).

Doses in eye lens, thyroid, and gonads, due to scattered radiation, during a CT radiodiagnosis study.

X-ray images used for radio-diagnosis are very useful to evaluate the progress of a treatment or to have a better diagnosis. However, during the interaction between the incoming X-ray beam and the body surface, part of the radiation is scattered out reaching other parts of the body delivering an undesirable dose. In this work the dose in eye lenses, thyroid, and gonads of a solid water phantom was measured using thermoluminescent dosimeters, while a Computer Tomography of the torso was obtained. With the measured absorbed dose the effective dose was calculated. Thus, the effective dose in the eye lens, thyroid, and gonads is approximately 57, 214 and 9 µSv respectively. The largest effective dose was on that area located nearest to the region where the radiation is scattered.

Comportamiento dosimétrico de un sistema de planificación mediante curvas de calibración de densidades electrónicas relativas / Dosimetric behaviour of a planning system through calibration curves of relative electron density

En esta investigación se planteó como objetivo la verificación del comportamiento dosimétrico del Sistema de Planificación de Tratamiento (TPS) de Radioterapia mediante las curvas de calibración de Densidades Electrónicas Relativas (DER). Este estudio se realizó en el Hospital de la Sociedad de Lucha Contra el Cáncer (SOLCA) Núcleo Loja, usando un fantoma antropomorfo CIRS 062M y un tomógrafo Toshiba Activion 16. Para determinar la nueva curva de calibración DER se tomaron los valores de densidades electrónicas especificadas en el manual del fantoma y las Unidades Hounsfield de la imagen tomográfica. Se realizó controles de calidad dosimétricos y verificación dosimétrica en tres casos clínicos: tórax, pelvis y cráneo; para realizar las pruebas dosimétricas se utilizó un acelerador CLINAC CX, cámara de ionización PTW tipo Farmer con volumen sensible de 0,6 cm3 y un electrómetro PTW UNIDOS E. Los resultados mostraron que las medidas para cada inserto del fantoma en ningún caso excedieron los límites establecidos de ± 20 UH, para el tomógrafo y el TPS; las pruebas de control de calidad no superaron el límite máximo de desviaciones en el cálculo de dosis absorbida por el TPS y la obtenida por medición de ± 4 % establecida por la IAEA y las verificaciones dosimétricas en tórax, pelvis y cráneo, determinaron que las desviaciones en el cálculo de la dosis absorbida por el TPS y la obtenida por medición no superaban la tolerancia del ± 5 % establecida por la ICRU.

In this research, the aim was to verify the dosimetric behavior of the Radiotherapy Treatment Planning System (TPS) using the Relative Electron Density (DER) calibration curves. This study was carried out at the SOLCA (Society of Fight Against Cancer) hospital in Loja, using an CIRS model 062M anthropomorphic phantom and a Toshiba Activion 16 tomograph. To determine the new DER calibration curve, the values of the electron densities specified in the manual of the phantom and the Hounsfield Units of the tomographic image were taken. Dosimetric quality controls were made in the location of three clinical cases: thorax pelvis and skull; used a CLINAC CX accelerator was used to perform the dosimetric tests, PTW ionization chamber type Farmer with sensitive volume of 0.6 cm3 and a PTW UNIDOS E electrometer. The results showed that the measurements for each insert of the phantom in no case exceeded the established limits of ± 20 UH, for the tomograph and the TPS; the quality control tests did not exceed the maximum limit of deviations in the calculation of dose absorbed by the TPS and the one obtained by measurement of ± 4% established by the IAEA and the clinical planning in the thorax, pelvis and skull, determine that the deviations in the calculation of the dose absorbed by the TPS and that obtained by measurement, they do not exceed the tolerance of ± 5% established by the ICR.

Dose calculation of radioactive nanoparticles: first considerations for the Design of Theranostic Agents.

The use of radioactive nanoparticles as imaging and therapeutic agents is increasing globally. Indeed, the use of these nanoparticles as perfect theranostic agent is highly anticipated in the pharmaceutical market. Among the radioactive nanoparticles, liposomes, solid lipid nanoparticles and polymeric nanoparticles are the most studied. However little information among adverse reactions, absorbed dose and correct dose to achieve the theranostic goal in a translational application is available. We developed a radioactive polymeric nanoparticle and calculated the absorbed dose in animal model (Wistar rats) using the OLINDA/EXM program. The results showed that some nanoparticle were uptake in five organs and minor elimination through the gastrointestinal and urinary pathways. The data corroborates the safe use in terms of blood-brain barrier and did not show high uptake by liver. The dosimetry data support the safe use of radioactive nanoparticles as theranostic agent. Graphical abstract ᅟ.

Metodología para la validación y el control del proceso de irradiación en una instalación autoblindada / Methodology for validation and control of irradiation process in a self-shielding gamma irradiator

Se desarrolló una metodología para la validación y el control de rutina del proceso de irradiación que se realiza en un irradiador autoblindado con fuentes de 60Co. Esta metodología fue aplicada a un irradiador modelo ISOGAMMA LLCo con el objetivo de garantizar la correcta explotación del equipo, la eficiencia de los servicios brindados y la obtención, en forma consistente, de un producto que cumpla con los atributos de calidad y las especificaciones predeterminadas

A methodology was developed for the validation and routine control of the irradiation process performed in a self-shielding gamma irradiator with 60Co sources. This methodology was applied to an irradiator model ISOGAMMA LLCo in order to ensure the proper operation of the equipment, efficiency of services provided and to consistently obtain, , a product that meets the quality attributes and default specifications

Verification of absorbed dose rates in reference beta radiation fields: Measurements with an extrapolation chamber and radiochromic film.

Beta Secondary Standard 2 (BSS 2) provides beta radiation fields with certified values of absorbed dose to tissue and the derived operational radiation protection quantities. As part of the quality assurance, the reliability of the CDTN BSS2 system was verified through measurements in the 90Sr/90Y and 85Kr beta radiation fields. Absorbed dose rates and their angular variation were measured with a 23392 model PTW extrapolation chamber and with Gafchromic radiochromic films on a PMMA slab phantom. The feasibility of using both methods was analyzed.

Fetus absorbed dose evaluation in head and neck radiotherapy procedures of pregnant patients.

In this work the head and neck cancer treatment of a pregnant patient was experimentally simulated. A female anthropomorphic Alderson phantom was used and the absorbed dose to the fetus was evaluated protecting the patient's abdomen with a 7cm lead layer and using no abdomen shielding. The target volume dose was 50Gy. The fetus doses evaluated with and without the lead shielding were, respectively, 0.52±0.039 and 0.88±0.052cGy.

Sistema computacional para dosimetria de nêutrons e fótons baseado em métodos estocásticos aplicado a radioterapia e radiologia / Stochastic method-based computational system for neutron/photon dosimetry applied to radiotherapy and radiology

OBJETIVO: Este artigo mostra um procedimento de conversão de imagens de tomografia computadorizada ou de ressonância magnética em modelo de voxels tridimensional para fim de dosimetria. Este modelo é uma representação personalizada do paciente que pode ser usado na simulação, via código MCNP (Monte Carlo N-Particle), de transporte de partículas nucleares, reproduzindo o processo estocástico de interação de partículas nucleares com os tecidos humanos. MATERIAIS E MÉTODOS: O sistema computacional desenvolvido, denominado SISCODES, é uma ferramenta para planejamento computacional tridimensional de tratamentos radioterápicos ou procedimentos radiológicos. Partindo de imagens tomográficas do paciente, o plano de tratamento é modelado e simulado. São então mostradas as doses absorvidas, por meio de curvas de isodoses superpostas ao modelo. O SISCODES acopla o modelo tridimensional ao código MCNP5, que simula o protocolo de exposição à radiação ionizante. RESULTADOS: O SISCODES vem sendo utilizado no grupo de pesquisa NRI/CNPq na criação de modelos de voxels antropomórficos e antropométricos que são acoplados ao código MCNP para modelar braquiterapias e teleterapias aplicadas a tumores em pulmões, pelve, coluna, cabeça, pescoço, e outros. Os módulos atualmente desenvolvidos no SISCODES são apresentados junto com casos exemplos de planejamento radioterápico. CONCLUSÃO: O SISCODES provê de maneira rápida a criação de modelos de voxels personalizados de qualquer paciente que podem ser usados em simulações por códigos estocásticos tipo MCNP. A combinação da simulação via MCNP com um modelo personalizado do paciente traz grandes melhorias na dosimetria de tratamentos radioterápicos.

OBJECTIVE: The present paper describes a procedure for conversion of computed tomography or magnetic resonance images into a three-dimensional voxel model for dosimetry purposes. Such model is a personalized representation of the patient that can be utilized in nuclear particle transport simulations by means of the MCNP (Monte Carlo N-Particle) code, reproducing the stochastic process of nuclear particles interaction with human tissues. MATERIALS AND METHODS: The developed computational system - SISCODES - is a tool designed for 3D planning of radiotherapy or radiological procedures. Based on tomographic images of the patient, the treatment plan is modeled and simulated. Then, the absorbed doses are shown by means of isodose curves superimposed on the model. The SISCODES couples the threedimensional model with the MCNP5 code, simulating the protocol of exposure to ionizing radiation. RESULTS: The SISCODES has been utilized by the NRI/CNPq in the creation of anthropomorphic and anthropometric voxel models which are coupled with the MCNP code for modeling brachytherapy and teletherapy applied to lung, pelvis, spine, head and neck tumors, among others. The current SISCODES modules are presented together with examples of cases of radiotherapy planning. CONCLUSION: The SISCODES provides a fast method to create personalized voxel models of any patient which can be used in stochastic simulations. The combination of the MCNP simulation with a personalized model of the patient increases the dosimetry accuracy in radiotherapy.