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Resumen Próximo a su 25 aniversario CENTIS reflexiona sobre su quehacer en el contexto de los trastornos que causa la COVID-19. Con ese propósito se examinan el estado de la medicina nuclear y la radiofarmacia antes y durante la epidemia y sus perspectivas de desarrollo. La producción global de radiofármacos continúa siendo una industria consolidada y aunque la pandemia afecta a esta esfera, la presencia de otras enfermedades no cesa, por lo que los servicios de medicina nuclear esenciales y críticos siguen siendo necesarios. Se espera su paulatina reapertura y que se retome con más fuerza la investigación, dado que la COVID-19 es tan compleja y se asocia a tantos factores que constituye, en perspectiva, terreno virgen para las técnicas diagnósticas en medicina nuclear. Ha de permanecer asimismo el papel de los radiofármacos terapéuticos en un grupo importante de enfermedades, en cáncer sobre todo. El Centro de Isótopos pone por ello énfasis tanto en la consolidación, bajo buenas prácticas, de la producción y el suministro de radiofármacos, como en el desarrollo de nuevos productos. Ambos aspectos se basan principalmente en dos radionúclidos: Tc-99m e Y-90.
Abstract Close to its 25th anniversary, CENTIS evaluates its work in the context of the disorders triggered by COVID-19. For this purpose, the situation of nuclear medicine and radiopharmacy, before and during the epidemic and their current development prospects is examined. The production of radiopharmaceuticals continues to be a consolidated global industry and although the pandemic affects this area, the presence of other diseases does not cease, so essential and critical nuclear medicine services are still needed, therefore its gradual reopening is expected. In addition, research will be taken with more strength, given that COVID-19 is so complex and associated with so many factors that it constitutes virgin terrain in perspective for diagnostic techniques in nuclear medicine. The role of therapeutic radiopharmaceuticals in an important set of diseases, especially cancer, will also remain. As a result, the Isotope Center focus its attention under good management practices, on the consolidation of the production and distribution of radiopharmaceuticals and in the development of new products. Both aspects are mainly based on two radionuclides: Tc-99m and Y-90.
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Resumen Para la obtención de radiotrazadores sólidos de 99mTc actualmente se necesitan nuevos soportes porosos. Estudios anteriores realizados por otros autores mostraron la posibilidad del marcaje con 99mTc de sedimentos de ríos con alto contenido de aluminosilicatos. En el presente trabajo se desarrolló una metodología para el marcaje de arena sílice con el 99mTcO4- para su uso como radiotrazador sólido. Se realizó el marcaje de la arena sílice previamente tratada y sin tratar empleando concentraciones variables de cloruro y fluoruro estañoso como agentes reductores y diferentes tiempos de marcaje. Se evaluó la influencia de la etapa de tratamiento previo de la arena en los rendimientos de retención del Tc obtenidos. Los cambios en la composición de la arena sílice luego de su tratamiento previo se pudieron constatar a partir de la Microscopía Electrónica de Barrido (SEM-EDS). Los resultados sugirieren el empleo de la arena sílice previamente tratada y de fluoruro estañoso como agente reductor, adicionalmente se propusieron modificaciones a la metodología inicial de tratamiento previo de la arena. Se pudo constatar a partir de la técnica SEM-EDS que el aumento del porciento de retención del Tc en la arena luego de su tratamiento, se debe fundamentalmente a los cambios observados en su composición química y en su estructura. Se logró la obtención de un radiotrazador sólido marcado con 99mTc en soporte de arena sílice con un tiempo de preparación estimado de 4 horas y un rendimiento de retención de 74%.
Abstract To obtain 99mTc solid radiotracers, new porous supports are currently needed. Previous studies carried out by other authors showed the possibility of 99mTc labeling of sediments from rivers with a high content of aluminosilicates. In the present work a methodology for labeling of silica sand with 99mTcO4- as a prospective solid radiotracer was developed. Labeling of the previously treated and untreated silica sand was carried out using variable concentrations of chloride and stannous fluoride as reducing agents and different labeling times. The influence of the pre-treatment stage of the sand on the obtained Tc retention yields was evaluated. The changes in the composition of the silica sand after its previous treatment could be verified from the Scanning Electron Microscopy (SEM-EDS). The results suggested the use of previously treated silica sand and stannous fluoride as a reducing agent, modifications were proposed to the initial methodology of previous treatment of the sand. It was possible to confirm from the SEM-EDS technique that the increase in the percentage of retention of Tc in the sand after its treatment is mainly due to the observed changes in its chemical composition and structure. It was possible to obtain a 99mTc solid radiotracer on support of silica sand with an estimated preparation time of 4 hours and a retention yield of 74%.
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Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.
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Animals , Male , Female , Mice , In Vitro Techniques , Technetium/pharmacology , Cidofovir/pharmacology , Track and Field/classification , Blood Circulation Time/adverse effects , Pharmaceutical Preparations/analysis , Kidney , MethodsABSTRACT
Abstract It is recognized worldwide that the security of radioactive substances is very important and that the design of facilities where these sources are used and stored must cater for the implementation of good security measures, including the shielding of some treatment and diagnostic rooms. The radiation protection assessment of a nuclear medicine facility consists of the evaluation of the annual effective dose both to workers occupationally exposed and to members of the public. This assessment take into account the radionuclides involved, the facility features, the working procedures, the expected number of patients per year, the administered activity, the distribution of rooms, the thickness and physical materials of walls, floors and ceilings and so on. The assessment results were compared to the design requirements established by the Cuban regulatory body in order to determine whether or not, the nuclear medicine facility complies with those requirements, both for workers and for members of the public. The work presented is useful for facility designer that uses unsealed radionuclides and for the regulatory body.
Resumen A nivel mundial se reconoce que la seguridad de las sustancias radiactivas es muy importante y que el diseño de las instalaciones, donde se utilizan y almacenan las mismas, tienen que implementar medidas de seguridad adecuadas, incluyendo el blindaje de algunos locales de tratamiento y diagnóstico. La evaluación de la protección radiológica de una instalación de medicina nuclear consiste en la determinación de la dosis efectiva anual, tanto para los trabajadores ocupacionalmente expuestos a las radiaciones como para los miembros del público. Esta evaluación tuvo en consideración los radionúclidos involucrados, las características de la instalación, los procedimientos de trabajo, la cantidad de pacientes que se espera tratar o diagnosticar por año, la actividad administrada, la distribución de los locales y el espesor de los materiales empleados en las paredes, pisos y techo, entre otros. Los resultados obtenidos de la evaluación fueron comparados con los requerimientos de diseño establecidos por el órgano regulador cubano para determinar si cumplen o no con tales requerimientos para los trabajadores expuestos y miembros del público. El trabajo presentado resulta útil para diseñadores de instalaciones que utilizan sustancias abiertas y para el órgano regulador.
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Objective To evaluate the diagnostic value of 99Tcm-MIBI SPECT/CT imaging and 99Tcm-MIBI planar imaging semi-quantitative analysis in primary hyperparathyroidism (PHPT).Methods A total of 89 patients were enrolled into this retrospective study.The diagnostic efficiencies of 99Tcm-MIBI SPECT/CT were compared with 9Tcm-MIBI planar scintigraphy and ultrasound,while the surgical pathology and the clinical follow-up results were considered as the standard.The region of interest extraction technique was used to measure and calculate the tumour to normal tissue ratios (T/NT) in the early and delayed phase of the planar scintigraphy,and the correlation between pathological type,PTH concentration and T/NT ratios was analyzed.Results The sensitivities and specificities of SPECT/CT,99Tcm-MIBI planar scintigraphy and ultrasound were 98.08％,88.46％,78.43％;82.93％,82.93％,58.82％ respectively.There were statistically significant correlations between the pathological type and PTH concentration,early phase T/NT and delayed phase T/NT,and the correlation coefficients r were 0.741,0.642 and 0.729,respectively.Conclusions 99Tcm-MIBI SPECT/CT imaging is an effective method for diagnosis of PHPT,with higher clinical application value than 99Tcm-MIBI planar scintigraphy and ultrasound.The semi-quantitative analysis of 99Tcm-MIBI planar scintigraphy provides a new method for the differential diagnosis of PHPT.
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@#AIM: To evaluate the clinical effects of using technetium-99 methylene diphosphonate(99Tc-MDP)with methylprednisolone to treat thyroid-associated ophthalmopathy(TAO). <p>METHODS: We retrieved from 9 databases, from their foundation to March 2019, including Pubmed, the Cochrane Library, EMbase, ClinicalTrial.gov, Web of Science, CNKl, VIP database, China Biology Medicine disc, Wanfang database and collected the randomized controlled trail(RCT)of 99Tc-MDP combined with methylprednisolone for treatment of TAO. According to inclusion and exclusion criteria, two researchers retrieved the literature independently, extracted data and evaluate methodological quality. Meta analysis was performed by Review Manager 5.3 software.<p>RESULTS: A total of 8 RCTs were identified with 644 patients. There was significant difference in the overall clinical effective rate between 99Tc-MDP combined with methylprednisolone and methylprednisolone alone(<i>RR</i>=1.14, 95% <i>CI</i>: 1.03-1.26, <i>P</i>=0.01). Significant difierence was found in the effective rate of proptosis between intravenous injection of 99Tc-MDP with methyprednisone and methyprednisone only(<i>RR</i>=1.28, <i>95% CI</i>: 1.16-1.41, <i>P</i><0.00001). Meanwhile, great improvement was seen in diplopia(<i>RR</i>=1.64, <i>95% CI</i>: 1.04-2.58, <i>P</i>=0.03), but there was no significant difference in disturbance of ocular dyskinesia(<i>P</i>=0.37).<p>CONCLUSION: Applying 99Tc-MDP combined with methylprednisolone is better than methylprednisolone alone for TAO with less adverse reaction, which appears to be an effective treatment for TAO.
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Objective To investigatethe significance of serum carbohydrate antigen (CA) 125,car cinoembryonic antigen (CEA),cytokeratin 19 fragment (CYFRA21-1),neuron-specific enolase (NSE),and squamous cell carcinoma antigen (SCCA) in the diagnosis of bone metastasis from lung cancer.Methods A total of 222 patients,including 91 lung cancer patients with bone metastasis (49 males,42 females,average age (60.07± 10.60) years;group A),75 lung cancerpatientswithout bone metastasis (57 males,18 females,average age (62.20± 12.63) years;group B),56 patients with benign lung diseases (34 males,22 females,average age (61.45± 10.66) years;group C) were recruited from January 2015 to January 2016.The electrochemiluminescence was applied to detect serum levels of CA125,CEA,CYFRA21-1,NSE and SCCA.Kruskal-Wallis,Wilcoxon rank sum test,x2 test and receiver operating characteristic (ROC) curve analysis were used to analyze data.Results The levels of serum CA125,CEA,CYFRA21-1,NSE in group A were higher than those in group B and C (H values:13.45-44.96,all P＜0.05);while SCCA was not significantly different among the 3 groups (H=2.56,P＞0.05).The areas under ROC curves for CA125,CEA,CYFRA21-1,NSE,SCCA were 0.667,0.702,0.602,0.664,0.440,respectively.The positive rate of serum NSE in small cell lung cancer (SCLC) patients was higher than that in non-small-cell lung cancer (NSCLC) patients (17/18 vs 32.88％ (24/73);x2=22.11,P＜0.05);CEA was highly expressed in adenocarcinoma,and SCCA was highly expressed in squamous cell carcinoma.Patients with grade Ⅲ+ Ⅳ metas tasis (n =52) had higher levels of CA 125,CEA,NSE compared to patients with Ⅰ + Ⅱ metastasis (n =39;z values:from-2.54 to-0.32,all P＜0.05).The sensitivity of combined detection of 5 tumor markers was 97.80％ (89/91),which was significantly higher than that of single tumor marker (x2 values:35.46-138.23,all P＜0.05).Conclusion Serum levels of CA125,CEA,CYFRA21-1,NSE and SCCA play a role in the diagnosis of bone metastasis from lung cancer,and the combined detection of the 5 tumor markers contribute to the early detection of bone metastases.
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Objective To compare the diagnostic efficiencies of different scanning schemes of dualphase 99Tcm-methoxyisobutylisonitrile (MIBI) planar imaging with or without SPECT/CT in the preoperative localization of parathyroid lesions.Methods Forty-two patients (20 males,22 females;average age (53.1 ± 14.8) years) with primary or secondary hyperparathyroidism who underwent parathyroidectomy from June 2011 to June 2016 were analyzed retrospectively.All patients underwent dual-phase 99Tcm-MIBI planar scan and dual-phase SPECT/CT scan.The images were collected according to the following 4 procedures:dualphase planar imaging (S1),dual-phase planar imaging+early-phase SPECT/CT (S2),dual-phase planar imaging+delayed-phase SPECT/CT (S3),dual-phase planar imaging+dual-phase SPECT/CT (S4).Pathological results were considered as the gold standard.A total of 168 parathyroid glands in 42 patients were evaluated by the 4 imaging procedures respectively.The diagnostic efficiencies were calculated and compared by x2 test.Results Seventy-eight abnormal parathyroid lesions were found.The diagnostic sensitivities of S1,S2,S3,S4 were 66.7％ (52/78),89.7％(70/78),69.2％(54/78),89.7％(70/78),and the accuracies were 78.6％ (132/168),94.0％ (158/168),85.1％ (143/168),94.0％ (158/168),respectively.The diagnostic accuracies of S2 and S4 were significantly higher than those of S1 and S3 (x2 values:17.027 and 7.176,both P＜0.01).Condusions The dual-phase planar imaging together with early-phase and dualphase SPECT/CT imaging have high diagnostic efficiencies in the preoperative localization of parathyroid lesions.Considering reducing radiation dose and examine time,the dual-phase planar imaging together with early-phase SPECT/CT is a better choice.
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El Tecnecio-99m es el radionúclido más utilizado en la actualidad en el campo de la medicina nuclear. El Centro Nacional de Seguridad Nuclear (CNSN) como órgano regulador de Cuba requiere la realización de análisis de riesgo a las instalaciones con peligro radiológico potencial asociado y preferentemente, que estos análisis sean realizados mediante el método de matriz de riesgo. Aunque existen varios métodos cualitativos o cuantitativos para realizar estos estudios, la existencia de bases de riesgo de partida y de códigos de análisis, así como la simplicidad de su empleo han privilegiado la matriz de riesgo como método semicuantitativo predominante. El artículo presenta los resultados de la aplicación de este método para la evaluación de los riesgos asociados a la producción de generadores de Molibdeno-99/Tecnecio-99m, que se realiza en el Centro de Isótopos (CENTIS). Empleando el código SECURE-MR Ver. 2.0 se realiza el análisis de riesgo detallado de la práctica. Se identificaron tres secuencias accidentales con nivel de riesgo alto y se determinó la importancia de barreras y reductores relacionados con factores humanos por suficiencia y capacitación de personal. Entre las aplicaciones derivadas del estudio se reportaron capacidades novedosas de análisis, así como posibilidades de monitoreo del riesgo. El modelo de riesgo desarrollado para el proceso de producción de generadores de Molibdeno-99/Tecnecio-99m unido a las capacidades de revisión, análisis y documentación ofrecidas por la herramienta permitieron la obtención de un documento coherente con el modelo, que constituye, además, una base de conocimientos efectiva para la evaluación de la seguridad de la instalación
Technetium-99m is the most commonly used radionuclide in the field of nuclear medicine. The National Center for Nuclear Safety (NCNS), as the regulatory body of Cuba, requires the carrying out of risk analysis for facilities with associated radiological hazard potential and, preferably, that these analyzes be performed using the risk matrix method. Although there are several qualitative or quantitative methods to perform these studies, the existence of basis risk starting and analysis codes and simplicity of use has been privileged the risk matrix as a predominant semi-quantitative method. The paper presents the results of the application of this method for the evaluation of the risks associated with the production of Molybdenum-99/Technetium-99m generators, which is carried out at the Isotope Center (Centis). Using the SECURE - MR Ver. 2.0 code a detailed risk analysis of its practice was carried out. Three accidental sequences of high-level risks were identified and the importance of barriers and reducers related to human factors associated to sufficiency and staff training was determined. Among the derived applications novel analysis capacities as well as risk monitoring possibilities are reported. The risk model developed for the production process of Molybdenum-99/Technetium-99m generators, joined with the ability to review, analyze and all the documentation provided by the tool, allow obtaining a completely and coherent document with the model, which constitutes an effective basis the safety of the facility
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PURPOSE: This study aimed to evaluate the relationships between 99mTecnicium-dimercaptosuccinic acid (DMSA) scan findings and clinical parameters including age and fever duration. METHODS: The positive rates for abnormal DMSA scans were analyzed according to the age of patients, fever duration prior to admission, and total fever duration. DMSA scan findings were divided into 3 categories: single defect, multifocal defects, and discrepant defects. We evaluated the detection rates of vesicoureteral reflux according to DMSA scan lesions. RESULTS: Among a total 320 cases, 141 (44.1%) had abnormal DMSA scans. The infant group (0-1 year of age) had a shorter total fever duration, and a lower C-reactive protein (CRP) value and DMSA positive rate (39.8% vs. 60.6%, P=0.002) compared to children group (2-15 years of age). Patients with abnormal scans had a longer total fever duration and higher CRP compared to those with normal scans. The positivity rate of abnormal scans did not differ between the patients with a short fever duration prior to admission of ≤2 days and those with longer fever duration of ≥3 days. However, patients with longer total fever duration had a higher rate of abnormal DMSA scans (P=0.02). Among cases with a single defect, multifocal defects, and discrepant defects, vesicoureteral reflux was observed in 22.4%, 60% and 70.6% of cases, respectively (P=0.004). CONCLUSION: Although DMSA scan has limitations in early diagnosis, DMSA scan findings may aid in the prediction of the severity of systemic inflammation and detection of vesicoureteral reflux.
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Child , Humans , Infant , C-Reactive Protein , Early Diagnosis , Fever , Inflammation , Pyelonephritis , Succimer , Urinary Tract Infections , Vesico-Ureteral RefluxABSTRACT
PURPOSE: This study aimed to evaluate the relationships between 99mTecnicium-dimercaptosuccinic acid (DMSA) scan findings and clinical parameters including age and fever duration. METHODS: The positive rates for abnormal DMSA scans were analyzed according to the age of patients, fever duration prior to admission, and total fever duration. DMSA scan findings were divided into 3 categories: single defect, multifocal defects, and discrepant defects. We evaluated the detection rates of vesicoureteral reflux according to DMSA scan lesions. RESULTS: Among a total 320 cases, 141 (44.1%) had abnormal DMSA scans. The infant group (0-1 year of age) had a shorter total fever duration, and a lower C-reactive protein (CRP) value and DMSA positive rate (39.8% vs. 60.6%, P=0.002) compared to children group (2-15 years of age). Patients with abnormal scans had a longer total fever duration and higher CRP compared to those with normal scans. The positivity rate of abnormal scans did not differ between the patients with a short fever duration prior to admission of ≤2 days and those with longer fever duration of ≥3 days. However, patients with longer total fever duration had a higher rate of abnormal DMSA scans (P=0.02). Among cases with a single defect, multifocal defects, and discrepant defects, vesicoureteral reflux was observed in 22.4%, 60% and 70.6% of cases, respectively (P=0.004). CONCLUSION: Although DMSA scan has limitations in early diagnosis, DMSA scan findings may aid in the prediction of the severity of systemic inflammation and detection of vesicoureteral reflux.
Subject(s)
Child , Humans , Infant , C-Reactive Protein , Early Diagnosis , Fever , Inflammation , Pyelonephritis , Succimer , Urinary Tract Infections , Vesico-Ureteral RefluxABSTRACT
Purpose To evaluate the clinical guiding value of 99Tcm-methoxyisobutylisonitrile gated myocardial perfusion imaging (99Tcm-MIBI G-MPI) in diagnosing the coronary microangiopathy in patients with diabetic mellitus.Materials and Methods Sixty patients with clinical confirmed coronary microvascular angina were selected and assigned into two groups,with 26 patients (with diabetes mellitus) in group A and 34 patients in group B (without diabetes mellitus).The region,extent and range of coronary microangiopathy was detected by 99Tcm-MIBI G-MPI,and the difference of myocardial ischemia between the two groups was statistically analyzed.Results The ratio of abnormal myocardial perfusion in group A was significantly higher than that in group B (96.15％ vs.73.53％,x2=5.43,P＜0.05);the total number of abnormal coronary branches in group A was significantly larger than that in group B (82.67％ vs.62.67％,P＜0.05);the total number abnormal perfusion segments in group A was significantly larger than that in group B (P＜0.05),and the abnormal perfusion segments number of anterior wall,septum,apical region and inferior wall in group A was significantly larger than that ingroup B (P＜0.05);the rate of abnormal perfusion at single coronary supplying region in group A was significantly lower than that in group B (P＜0.05).Conclusion 99Tcm-MIBI G-MPI is of great clinical significance for diagnosing coronary microangiopathy and evaluating myocardial ischemia in patients with diabetes mellitus.
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OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.
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Animals , Female , Mice , Bone-Implant Interface/physiology , Organotechnetium Compounds , Osteonecrosis/physiopathology , Peptides, Cyclic , Radiopharmaceuticals , Bone Transplantation , Diphosphonates , Disease Models, Animal , Femur/pathology , Femur/physiopathology , Isotope Labeling/methods , Neovascularization, Physiologic/physiology , Osteonecrosis/pathology , Reproducibility of Results , Time Factors , Tissue Survival/physiology , Tomography, X-Ray ComputedABSTRACT
Objective To evaluate the value of technetium-99m methoxy isobutyl isonitrile (99Tcm-MIBI)tomography and integrated CT in preoperative localization diagnosis of secondary hyperparathyroidism (SHPT).Methods 28 patients with SHPT were selected.15 minutes and 90 minutes (delayed images)after intravenous administration of 99Tcm-MIBI 370 MBq,static anterior planar images of the neck and chest were obtained.99Tcm-MIBI tomography and integrated CT scan were acquired after the delayed imaging.The imaging findings were compared to the pathological results.Results The detection rate of SHPT lesions by 99Tcm-MIBI dua-phase imaging and 99Tcm-MIBI tomography and registration with integrated CT scan was 53.3％ and 70.7％ respectively.The difference had statistical significance(X2 =5.903,P＜0.05).The fusion imaging with integrated CT can provide detailed anatomy data and more information for surgical doctors.Conclusion 99Tcm-MIBI tomography and registration with integrated CT scan can improve the detection rate of SHPT compared with 99Tcm-MIBI dua-phase imaging,provide more detailed anatomy data,and has high clinical value in preoperative localization and diagnosis of SHPT.
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The most common manifestation of multiple endocrine neoplasia type 1 (MEN1) is hyperparathyroidism. Treatment of hyperparathyroidism in MEN patients is surgical removal of the parathyroid glands, however ectopic parathyroid gland is challenging for treatment. A 51-year-old female, the eldest of 3 MEN1 sisters, had hyperparathyroidism with ectopic parathyroid adenoma in the mediastinal para-aortic region, which was detected by technetium-99m (Tc-99m) sestamibi scintigraphy and single-photon emission computed tomography/computed tomography (SPECT/CT). She underwent total parathyroidectomy with video-assisted thoracoscopic surgery on an anterior mediastinal mass. Anterior mediastinal parathyroid adenoma in MEN1 patients is rare. Precise localization of an ectopic parathyroid gland with Tc-99m sestamibi SPECT/CT can lead to successful treatment of hyperparathyroidism. This is the first reported case in the literature of mediastinal parathyroid adenoma in MEN1 patient visualized by Tc-99m sestamibi SPECT/CT.
Subject(s)
Female , Humans , Male , Middle Aged , Hyperparathyroidism , Multiple Endocrine Neoplasia Type 1 , Multiple Endocrine Neoplasia , Parathyroid Glands , Parathyroid Neoplasms , Parathyroidectomy , Radionuclide Imaging , Siblings , Thoracic Surgery, Video-Assisted , Tomography, Emission-Computed, Single-PhotonABSTRACT
Background Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol.L−1 (S. aureus) and 10.10 μmol.L−1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.(AU)
Subject(s)
Peptides , Chelating Agents , Anti-Infective Agents , Technetium/analysisABSTRACT
Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with 99mTc. Methods Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with 99mTc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2. 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values 0.05). Results Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 mol.L1 (S. aureus) and 10.10 mol.L1 (E. coli). Thus, only the latter was radiolabeled with 99mTc. The radiochemical purity analysis of LyeTx I-K-HYNIC-99mTc showed that the optimal radiolabeling conditions (10 g of LyeTx I-K-HYNIC; 250 g of SnCl2. 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n= 3). However, RP-HPLC data suggested 99mTc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). Conclusions The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.
Subject(s)
Anti-Infective Agents/analysis , Anti-Infective Agents/chemistry , Intercellular Signaling Peptides and Proteins/analysisABSTRACT
Las tecnologías de radiotrazadores y de escaneo son herramientas bien consolidadas para el estudio, análisis y evaluación de los procesos industriales y medioambientales. En este trabajo se sintetizan los principales resultados alcanzados por el Grupo de Aplicaciones Industriales y Medioambientales de los Radiotrazadores en el Departamento de Radioquímica. La tecnología de radiotrazadores se ha empleado con éxito para la caracterización del mezclado en reactores discontinuos, los estudios sobre el comportamiento del 99mTc en aguas naturales y residuales, la calibración y validación del modelo de calidad de agua del río Almendares, la caracterización de un reactor anaerobio para el tratamiento de los residuales en el CAI Pablo Noriega, la verificación y validación del modelo DFC en un cristalizador azucarero, el desarrollo de un generador radisotópico de ? / ?, la modelación de la calidad del agua en el segmento medio del río Luyanó, y para la modelación de la calidad del agua en el río Guaire, Caracas, Venezuela. En los últimos años el grupo ha desarrollado y evaluado a nivel de laboratorio radiotrazadores para fluidos orgánicos, particularmente relacionados con la industria del petróleo y para sólidos, empleando como precursor al ?. Mientras la técnica de escaneo se ha utilizado para el perfilaje gamma en torres de destilación de alcohol de los CAI "Héctor MolinaHeriberto Duquesne" y "Jesús Rabí".
ABSTRACT
Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI)6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol:chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI)6]+ since impurities such as99mTc-reduced-hydrolyzed (RH),99mTcO4- and [99mTc(cysteine)2]-complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.
Subject(s)
Chromatography, Paper/methods , Chromatography, Thin Layer/methods , Radiopharmaceuticals/analysis , /analysis , Alcohols , Chloroform , Chromatography, Paper/economics , Chromatography, Thin Layer/economics , Chromatography/economics , Chromatography/methods , Quality Control , Radiopharmaceuticals/classificationABSTRACT
RESUMO Ricinus communisé uma planta pertence à família Euforbiaceae. A partir de seus frutos é extraído o óleo de rícino e outra fração altamente tóxica (fração não-oleosa). Neste estudo, foi avaliado o efeito da fração não oleosa de R. communis(FNORC) na biodistribuição do Tc-99m em camundongos sadios e em animais transplantados com Sarcoma-180 (S180). Para avaliação da biodistribuição do Tc-99m, o percentual de atividade radioativa total injetada (ATI%) foi mensurada utilizando um contador gama. Os resultados mostraram que, em animais sadios, houve aumento da captação do Tc-99m após o tratamento com FNORC pelos rins, cérebro e estômago. Apenas houve diminuição da absorção deste radioisótopo nos músculos. Em animais com tumor, houve redução significativa da captação do Tc-99m no coração, pulmões e tumor, e foi observado o aumento da captação apenas nos rins. Foi observada também a diminuição da concentração das proteínas plasmáticas totais em animais com tumor após tratamento com FNORC e atividade antitumoral significativa. Diante desses dados, conclui-se que fração não oleosa de R. communis possui atividade antitumoral significativa, porém altera a biodistribuição do Tc-99m, fato este que pode resultar em falhas nos processos de diagnóstico por imagem que utilizem este radioisótopo como marcador.
ABSTRACT Ricinus communis is a plant belonging to the Euforbiaceae family. From its fruits, it is extracted the castor oil and another highly toxic fraction (non-oily fraction). In this study, we evaluated the effect of the non-oily fraction of R. communis (NOFRC) on the bio distribution of Tc-99m in healthy mice and in animals transplanted with Sarcoma-180 (S180). To evaluate the bio distribution of theTc-99m, the percentage of the total injected radioactivity (% TIR) was measured through a gamma counter. There was an increase in the capitation of Tc-99m after the treatment with NOFRC in the kidneys, brain, and stomach of healthy animals. A decrease in the reception of this radionuclide was only found in the muscles. In animals with tumour, there was a significant reduction in the uptake of Tc-99m in the heart, lungs and tumour. An increase in the capitation was only observed in the kidneys. It was also observed a reduction in the total plasma protein concentration in animals with tumours after the treatment with NOFRC, besides significant antitumor activity. We concluded that there is antitumor activity in the NOFRC, but that it alters the biodistribution of Tc-99m, a fact which may result in failures in the diagnostic imaging process using this radioisotope as a marker.