Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study.

Implementation of radiopharmaceutical therapy dosimetry varies depending on the clinical application, dosimetry protocol, software, and ultimately the operator. Assessing clinical dosimetry accuracy and precision is therefore a challenging task. This work emphasizes some pitfalls encountered during a structured analysis, performed on a single-patient dataset consisting of SPECT/CT images by various participants using a standard protocol and clinically approved commercial software. Methods: The clinical dataset consisted of the dosimetric study of a patient administered with [177Lu]Lu-DOTATATE at Tygerberg Hospital, South Africa, as a part of International Atomic Energy Agency-coordinated research project E23005. SPECT/CT images were acquired at 5 time points postinjection. Patient and calibration images were reconstructed on a workstation, and a calibration factor of 122.6 Bq/count was derived independently and provided to the participants. A standard dosimetric protocol was defined, and PLANETDose (version 3.1.1) software was installed at 9 centers to perform the dosimetry of 3 treatment cycles. The protocol included rigid image registration, segmentation (semimanual for organs, activity threshold for tumors), and dose voxel kernel convolution of activity followed by absorbed dose (AD) rate integration to obtain the ADs. Iterations of the protocol were performed by participants individually and within collective training, the results of which were analyzed for dosimetric variability, as well as for quality assurance and error analysis. Intermediary checkpoints were developed to understand possible sources of variation and to differentiate user error from legitimate user variability. Results: Initial dosimetric results for organs (liver and kidneys) and lesions showed considerable interoperator variability. Not only was the generation of intermediate checkpoints such as total counts, volumes, and activity required, but also activity-to-count ratio, activity concentration, and AD rate-to-activity concentration ratio to determine the source of variability. Conclusion: When the same patient dataset was analyzed using the same dosimetry procedure and software, significant disparities were observed in the results despite multiple sessions of training and feedback. Variations due to human error could be minimized or avoided by performing intensive training sessions, establishing intermediate checkpoints, conducting sanity checks, and cross-validating results across physicists or with standardized datasets. This finding promotes the development of quality assurance in clinical dosimetry.

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.

Discharges of Nuclear Medicine Radioisotopes: The Impact of an Abatement System.

ABSTRACT: Clinical uses of radiopharmaceuticals imply the administration of radioactive substances that are mainly excreted through urine. The Nuclear Medicine Department at the Instituto Nacional de Cancerología (INC-COL) in Bogota, Colombia, administers radiopharmaceuticals for diagnostics and treatment to many patients, resulting in tens of cubic meters of radioactive waste water (WW) every day. As Colombian regulatory limits for liquid radioactive discharges to the sewer system are lower than in other countries, longer WW decay times are required, even when an in-house waste water treatment plant (WWTP) is used. To fulfill the requirements for controlled disposal of radioactive discharges, a complementary abatement system was implemented to retain WW for periods as long as 360 d, and was connected to the hospital´s WWTP. These holding times can cause major changes in the WW physicochemical parameters, reaching levels higher than acceptable. In this study, we evaluate the decontamination and decay efficiency of the retention system using water quality parameters and the amount of radioactivity in the effluents stored in the tanks and the WWTP. According to the results, to maintain the physicochemical parameters below acceptable levels, biological and chemical treatment of decayed WW is necessary before discharging it into urban waste water. Using the principles of dilution, retention, and decay, an integral radioactive WW management system was implemented favoring the quality of discharges and activity levels to the sewer system, with efficiencies close to 100% for WW from discharges in diagnostic procedures ranging from 98% (131I) to 100% (177Lu) for WW from discharges in therapeutic procedures. Activity concentration assessment in medically-derived radionuclides using an in-house waste water treatment plant (WWTP) and a complementary abatement system; an in-house WWTP could be used as an abatement system for short-lived radionuclides; and a tank-based abatement system attached to the in-house WWTP showed higher efficiencies for long-lived radionuclides and adequate physicochemical parameters for the discharge to the city sewage system.

Regulation of nuclear medicine services: Perception of the problems and challenges in Colombia for the approach to cancer / Regulación de los servicios de medicina nuclear: percepción de la problemática y desafíos para el manejo del cáncer en Colombia

Introduction: Colombia has modified the nuclear medicine norms that impact the administration of radioactive iodine therapy in the treatment of thyroid cancer. Objective: To identify the areas of agreement regarding the issue, as well as the current and emergent requirements associated with the normative for the operation of nuclear medicine services that have an impact on the care of patients with thyroid cancer in Colombia. Materials and methods: We conducted a two-round Delphi study for each expert, clinical, and regulatory group. The first round explored views on the implications of the regulations that apply to nuclear medicine. The second round rated the statements from the first round by their relevance. Results: The issues regarding nuclear medicine services were related to the normative clarity and the lack of synergy and coherence among inspection, surveillance, and control bodies. The demands on the waste management system require a high economic investment that can influence the service offer and have an impact on the integral control of thyroid cancer. Unification of the auditors' criteria, delimitation of the acting agent functions, technical assistance to the services to comply with the normative, and the oversight of the inspection, surveillance, and control bodies by the regulatory entities are among the current and future needs. Conclusions: Our findings suggest that nuclear medicine services are going through a time of multiple institutional, regulatory, and economic challenges that put at risk the development and maintenance of nuclear medicine in cancer care.

Introducción. La modificación de las normas sobre medicina nuclear en Colombia ha afectado la administración de la terapia de yodo radioactivo en el tratamiento del cáncer de tiroides. Objetivos. Determinar las áreas de acuerdo en torno al problema, los requisitos actuales y los nuevos exigidos en la normativa para el funcionamiento de los servicios de medicina nuclear. Materiales y métodos. Se hizo un estudio Delphi de dos rondas con cada grupo de expertos, 'clínicos' y 'de entidades reguladoras'. En la primera ronda se exploraron los puntos de vista sobre las implicaciones de la normativa en medicina nuclear y, en la segunda, se calificaron las declaraciones de la primera según su relevancia. Resultados. La problemática de los servicios de medicina nuclear está relacionada con la claridad normativa, y la falta de sinergia y coherencia entre los organismos de inspección, vigilancia y control. Las exigencias del sistema de gestión de desechos requieren una alta inversión económica que puede influir en la oferta del servicio y repercutir en el control integral del cáncer de tiroides. Entre las necesidades presentes y futuras, se encuentran la unificación de criterios entre los auditores, la delimitación de funciones de los actuantes, la asistencia técnica para cumplir con la normativa, y la veeduría a los organismos de inspección, vigilancia y control por parte de los entes reguladores. Conclusión. Los hallazgos del estudio sugieren que los servicios de medicina nuclear atraviesan un momento de múltiples desafíos institucionales, normativos y económicos, que ponen en riesgo el desarrollo y mantenimiento de la medicina nuclear en la atención oncológica.

Regulación de los servicios de medicina nuclear: percepción de la problemática y desafíos para el manejo del cáncer en Colombia / Regulation of nuclear medicine services: Perception of the problems and challenges in Colombia for the approach to cancer

Resumen | Introducción. La modificación de las normas sobre medicina nuclear en Colombia ha afectado la administración de la terapia de yodo radioactivo en el tratamiento del cáncer de tiroides. Objetivos. Determinar las áreas de acuerdo en torno al problema, los requisitos actuales y los nuevos exigidos en la normativa para el funcionamiento de los servicios de medicina nuclear. Materiales y métodos. Se hizo un estudio Delphi de dos rondas con cada grupo de expertos, 'clínicos' y 'de entidades reguladoras'. En la primera ronda se exploraron los puntos de vista sobre las implicaciones de la normativa en medicina nuclear y, en la segunda, se calificaron las declaraciones de la primera según su relevancia. Resultados. La problemática de los servicios de medicina nuclear está relacionada con la claridad normativa, y la falta de sinergia y coherencia entre los organismos de inspección, vigilancia y control. Las exigencias del sistema de gestión de desechos requieren una alta inversión económica que puede influir en la oferta del servicio y repercutir en el control integral del cáncer de tiroides. Entre las necesidades presentes y futuras, se encuentran la unificación de criterios entre los auditores, la delimitación de funciones de los actuantes, la asistencia técnica para cumplir con la normativa, y la veeduría a los organismos de inspección, vigilancia y control por parte de los entes reguladores. Conclusión. Los hallazgos del estudio sugieren que los servicios de medicina nuclear atraviesan un momento de múltiples desafíos institucionales, normativos y económicos, que ponen en riesgo el desarrollo y mantenimiento de la medicina nuclear en la atención oncológica.

Abstract | Introduction: Colombia has modified the nuclear medicine norms that impact the administration of radioactive iodine therapy in the treatment of thyroid cancer. Objective: To identify the areas of agreement regarding the issue, as well as the current and emergent requirements associated with the normative for the operation of nuclear medicine services that have an impact on the care of patients with thyroid cancer in Colombia. Materials and methods: We conducted a two-round Delphi study for each expert, clinical, and regulatory group. The first round explored views on the implications of the regulations that apply to nuclear medicine. The second round rated the statements from the first round by their relevance. Results: The issues regarding nuclear medicine services were related to the normative clarity and the lack of synergy and coherence among inspection, surveillance, and control bodies. The demands on the waste management system require a high economic investment that can influence the service offer and have an impact on the integral control of thyroid cancer. Unification of the auditors' criteria, delimitation of the acting agent functions, technical assistance to the services to comply with the normative, and the oversight of the inspection, surveillance, and control bodies by the regulatory entities are among the current and future needs. Conclusions: Our findings suggest that nuclear medicine services are going through a time of multiple institutional, regulatory, and economic challenges that put at risk the development and maintenance of nuclear medicine in cancer care.

Eficacia de lutecio-177 DOTATATE/TOC en pacientes con tumores neuroendocrinos bien diferenciados en estado avanzado. Ensayo clínico fase II / Efficacy of Lutetium-177 DOTATATE/TOC in Advanced Neuroendocrine Tumors

Resumen Introducción: En 2009, el Instituto Nacional de Cancerología (INC) elaboró el 177Lu-DOTATATE/TOC. El propósito del estudio fue demostrar la eficacia de estos radiopéptidos en el tratamiento paliativo de pacientes con tumores neuroendocrinos (TNE) avanzados inoperables (metastásicos o localmente avanzados) y en progresión. Métodos: Ensayo clínico abierto fase II de un solo brazo en 13 pacientes adultos con TNE grado 1 o 2, con expresión de receptores de somatostatina en lesiones blanco demostrada por captación Krenning 3 o 4 en 99mTc-HYNIC TOC. Los pacientes fueron tratados con 177Lu-DOTATATE o 177Lu-DOTATOC (según disponibilidad) a una actividad acumulativa proyectada de 600-800 mCi dividida en 3-4 dosis cada 6-9 semanas comenzando siempre con una actividad fija de 200 mCi y dosimetría con la primera dosis. El desenlace primario fue la respuesta objetiva calculada 6 y 12 meses después de la última dosis del tratamiento. Resultados: Se incluyeron 13 pacientes (7 mujeres) de 63 ± 11,6 años con TNE avanzado inoperable y en progresión. La actividad final administrada fue de 800 mCi, 600 mCi, 400 mCi y 200 mCi en 4, 7, 1 y 1 pacientes, respectivamente. La tasa de control de enfermedad a 6 y 12 meses fue de 69,2% y 45,5%, respectivamente, logrando únicamente enfermedad estable. Fallecieron 7 pacientes, 2 de ellos en los primeros 6 meses. La mediana de supervivencia global a partir de la última dosis del radiopéptido fue de 15,7 meses. Conclusiones: Se corroboró la eficacia y la seguridad del tratamiento con los radiopéptidos en NETs avanzados.

Abstract Objectives: The National Cancer Institute first elaborated 177Lu-DOTATATE/TOC in 2009. The purpose of this study was to prove the efficacy of these radiopeptides in the palliative treatment of patients with progressive advanced inoperable neuroendocrine tumors (NETs). Methods: A single-phase phase II open clinical trial was conducted in 13 adult patients with grade 1 y 2 NETs, with expression of somatostatin receptors in target lesions proven by Krenning Score 3 or 4 uptake in 99mTc-HYNIC TOC. Patients were treated with 177Lu-DOTATATE or 177Lu-DOTATOC (depending upon availability) at a projected acumulative activitiy of 600-800 mCi divided into 3-4 doses every 6-9 weeks always beginning with a fixed activity of 200 mCi and dosimetry during the first dose. The primary outcome was objective response to therapy. Results: 13 patients (7 women) aged 63 ± 11.6 years with inoperable advanced NETs were included. The final therapeutic administered activity was 800 mCi, 600 mCi, 400 mCi and 200 mCi in 4, 7, 1 and 1 patients, respectively. The disease control rate at 6 and 12 months was 69.2% and 45.5%, respectively, only obtaining stable disease. Six patients died, 2 of them in the first 6 months. Median overall survival was 15.7 months from the last treatment dose. Conclusions: The efficacy of the treatment with 177Lu-DOTATATE or 177Lu-DOTATOC radiopeptides elaborated in-house was confirmed, becoming a management alternative for patients with advanced NETs.

Análisis de espectros de resonancia magnética / Magnetic resonance spectrum analysis

Objetivo: Estudiar el comportamiento del uso de razones entre metabolitos y de la comparación de un volumen de interés con uno contralateral para determinar cuál de estas 2 técnicas es la más apropiada para obtener una relación del comportamiento metabólico de un espectro de resonancia magnética. Métodos: Fueron reclutados 10 voluntarios sanos, en los que fueron analizados el lóbulo parietal, el lóbulo temporal y los ganglios basales. Resultados: La cuantificación directa del espectro mostró un mayor coeficiente de variación dentro de los análisis realizados, lo cual justifica usar técnicas con referentes endógenos. El estudio de un volumen contralateral mostró ser una técnica con dispersión e índice de lateralidad altos. El uso de la creatina (Cr) como metabolito de control presentó un coeficiente de variación menor que la primera técnica evaluada. Los resultados hallados (ganglios basales: n-acetil-aspartato/Cr: 3 ± 6; colina/Cr: 2 ± 4. Lóbulo temporal: N-acetil-aspartato/Cr: 5 ± 5; colina/Cr: 8 ± 12. Lóbulo parietal: N-acetil-aspartato/Cr: 2,0 ± 0,6; colina/Cr: 0,9 ± 0,5) muestran valores similares a los encontrados en la literatura, con variaciones regionales considerables. Conclusiones: La técnica de cuantificación de la razón de los metabolitos con la Cr es la más adecuada para usar en el Instituto Nacional de Cancerología, por tener una dispersión menor y por arrojar valores cercanos a los reportados en la literatura en las diferentes regiones anatómicas estudiadas.

Objective: To study the performance in the use of metabolite ratios and the comparison of a contralateral volume of interest in order to determine which of these two techniques is most suitable for obtaining a ratio of the metabolite behaviour of a magnetic resonance spectrum. Methods: The parietal lobe, the temporal lobe, and basal ganglions were analysed in the 10 healthy volunteers included in the study. Results: The direct quantification of the spectra showed a wide coefficient of variation within the analyses performed, which justified using techniques with endogenous references. The study of a contralateral volume showed to be a technique with a high dispersion and laterality index. The use of creatinine (Cr) as a control metabolite had a lower coefficient of variation than the first technique evaluated. The results obtained (basal ganglions: N-acetyl-aspartate/Cr: 3 ± 6; choline/Cr: 2 ± 4. Temporal lobe: N-acetyl-aspartate/Cr: 5 ± 5; choline/Cr: 8 ± 12. Parietal Lobe: N-acetyl-aspartate/Cr: 2.0 ± 0.6; choline/Cr: 0.9 ± 0.5) showed similar values to those obtained in the literature, with considerable anatomical region variations. Conclusions: The technique that measures the ratio of the metabolites with Cr is the most suitable for use in the Instituto Nacional de Cancerología (National Oncology Institute), due to having a lower dispersion and producing results near those repo rted in the literature in the different anatomical regions studied.

Efectos biológicos y aspectos de seguridad de las radiaciones no ionizantes en la resonancia magnética / Non-Ionizing Biological Effects and Security Issues in Magnetic Resonance

Objetivo: Hacer una revisión, en español, de los efectos biológicos determinísticos de los campos magnéticos estáticos, dinámicos y de radiofrecuencia, propios de los exámenes de resonancia magnética (RM) en hospitales. Metodología: Se hace referencia a los límites definidos dependiendo de los distintos usos de la radiofrecuencia en un examen de RM y sus posibles efectos biológicos. Además, se muestran los aspectos de seguridad que deben tenerse en cuenta cuando se diseñan zonas que incluyan esta técnica diagnóstica. Finalmente, se hace una breve revisión de los temas que deben tener en cuenta los entes reguladores ante este tipo de exámenes con radiaciones no ionizantes. Conclusiones: A pesar de no ser determinantes los estudios sobre riesgo biológico, sí hay riesgos, principalmente por la existencia de altos campos magnéticos, que aconsejan tener ciertas precauciones en cuanto a instalaciones y personal calificado, así como una legislación acorde, de la que, por otra parte, carece Colombia.

Objective: To review the deterministic biological effects of static, dynamic and dependent magnetic fields used in clinical magnetic resonance imaging (MRI). Methods: The suggested limits are referenced depending on the different MRI applications, as well as their possible biological effects. In addition, safety aspects which must be taken into account when areas that include this diagnostic technique are shown. Lastly, a short description of the important items for the regulatory authorities to consider when facing these types of test with non-ionizing radiation is discussed. Conclusions: Even though there is no agreement in the literature about the biological risks, risks do exist due to the presence of high magnetic fields. Specific precautions should be taken in terms of proper facilities and qualified personnel, as well as an appropriate legislation which does not exist in Colombia.