Centro de Isótopos: acciones en beneficio de la salud pública / Center of Isotope: actions for the benefit of public health

RESUMEN En tributo a los cinco siglos de ciudad el Centro de Isótopos hace recuento de su actividad. La obtención de compuestos marcados con radionucleidos y otros trabajos radioquímicos en el Instituto de Física Nuclear, inaugurado en 1969, estimularon las aplicaciones de las fuentes radiactivas abiertas, por lo que puede considerarse el antecedente organizado más palpable del centro. Posteriormente en los años 80, la Secretaria Ejecutiva para Asuntos Nucleares aceleró, diversificó y amplió las aplicaciones, desarrolló la formación de cuadros y especialistas y la colaboración internacional. La puesta en operación del Centro de Estudios Aplicados al Desarrollo de la Energía Nuclear coincidió con la consolidación de un grupo de instituciones de investigación y producción biotecnológica y con el auge de las aplicaciones en Medicina Nuclear. Pronto se reconoció que no era posible continuar el manejo de un inventario cada vez mayor de radionucleidos, por lo que se diseñó y construyó un centro especializado a ciclo completo: investigación-desarrollo, producción y comercialización, el CENTIS. Durante su integración en 1994 a la Agencia de Energía Nuclear, se concluyó la inversión y se establecieron las metodologías de producción de los más importantes radiofármacos. En más de 20 años de labor CENTIS se ha convertido en el principal soporte de la Medicina Nuclear del país. Con sus capacidades metrológicas en la magnitud radiactividad y sus investigaciones no clínicas y clínicas, se inserta de forma cada vez más estrecha en la vida socio-económica del país y su capital. En el trabajo se detallan los principales resultados de cada etapa en lo relacionado a la misión del centro y se hace una valoración técnica de hacia dónde se encaminan acciones en favor de sus sectores destino: salud e investigación biomédica. Lustros en favor de siglos.

ABSTRACT To commemorate the 500th anniversary of the city of Havana, the Isotope Center reviews its activity since its creation. The production of radionuclidemarked compounds and other radiochemical work at the Institute of Nuclear Physics, inaugurated in 1969, stimulated the applications of open radioactive sources, which can be considered as the most tangible organized antecedent of the center. Later in the 1980s, the Executive Secretary for Nuclear Affairs accelerated, diversified and expanded nuclear applications, developed the training of highly qualified staff and experts as well as international cooperation. The creation of the Center for Applied Nuclear Development Studies coincided with the consolidation of a group of biotechnological research and production institutions and with these applications gaining importance in Nuclear Medicine. It was soon recognized that it was not possible to continue managing a growing inventory of radionuclides. As a result, CENTIS, a specialized center with a complete cycle, was designed and built, which comprised not only research and development, but also production and marketing. When in 1994 CENTIS became part of the Nuclear Energy Agency, investment was concluded and the production methodologies of the most important radiopharmaceuticals were established. In more than 20 years of work CENTIS has become the main support of Nuclear Medicine in the country. With its metrological capabilities in the magnitude of radioactivity and its non-clinical and clinical research, it is increasingly part of the socio-economic life of the country and its capital. In this paper the main results of each stage are detailed in relation to the mission of the center and a technical assessment is made regarding the actions taken to favor their target sectors: health and biomedical research. Periods of five years in favor of centuries.

Estudio comparativo de la biodistribución de 99mTc-HYNIC-Lys3-bombesina obtenido con los coligandos EDDA/tricina y AN/tricina / Comparative study of the biodistribution of 99mTc-HYNIC-Lys3-Bombesin obtained with the EDDA/tricine and NA/tricine as coligands

El propósito de la presente investigación fue evaluar la biodistribución en animales sanos y en modelos de tumores de los radiofármacos 99mTc-EDDA/tricina-HYNIC-Lys3-bombesina (HYNIC-Lys3-BN) y 99mTc-AN/tricina-HYNIC-Lys3-BN. La biodistribución y la farmacocinética fueron realizados durante 24 horas para lo cual se utilizaron 24 ratas wistar sanas a las cuales se les administró 37,0±0,8 MBq/rata de cada radiofármaco y para el estudio de modelo de tumor fueron utilizados 20 ratones desnudos CD-1 a los que se les injertaron tumores de próstata (PC3). Diez días después fueron calculados los volúmenes tumorales y aplicados 40,00±0,04 MBq/ratón de cada radiofármaco. Ambos mostraron alta pureza radioquímica con valores de 98,08±0,25% para el compuesto con EDDA/tricina y de 95,1±0,3% para el conjugado con AN/tricina. La captación del radiofármaco con AN/tricina fue significativamente mayor en órganos del sistema retículo endotelial de ratas Wistar sanas durante 24h, específicamente en hígado y bazo. No se encontraron diferencias significativas entre los tiempos medios de eliminación de la sangre para ambos compuestos. El volumen promedio de crecimiento tumoral fue 0,93±0,02cm3 y la afinidad por tumores mostró una unión creciente y específica de ambos radiofármacos, siendo significativamente mayor para el conjugado con EDDA/tricina. Este resultado permitió corroborar la relación directa que existe entre la densidad de receptores del péptido liberador de la gastrina (PLGr) y la variación de la acumulación de los radiofármacos en el tumor. El uso de EDDA/tricina como coligando para marcar HYNIC-Lys3-BN con 99mTc, es más apropiado que AN/tricina(AU)

The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals 99mTc-EDDA/tricine-HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and 99mTc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24hours. To do so, 24 healthy Wistar rats were used and were administered 37.0±0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00±0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08±0.25% for EDDA/tricine product and 95.1±0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93± 0.02cm3 and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with 99mTc(AU)

[Comparative study of the biodistribution of (99m)Tc-HYNIC-Lys3-Bombesin obtained with the EDDA/tricine and NA/tricine as coligands]. / Estudio comparativo de la biodistribución de (99m)Tc-HYNIC-Lys3-bombesina obtenido con los coligandos EDDA/tricina y AN/tricina.

The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals (99m)Tc-EDDA/tricine-HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and (99m)Tc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24 hours. To do so, 24 healthy Wistar rats were used and were administered 37.0 ± 0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00 ± 0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08 ± 0.25% for EDDA/tricine product and 95.1 ± 0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93 ± 0.02 cm(3) and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with (99m)Tc.

Nueva formulación para marcar ciprofloxacina con 99mTc / New formulation to label ciprofloxacin with 99mTc

No disponible

[Value of scintigraphy with 99mTc-MIBI in the diagnosis and follow-up of Hodgkin's and non-Hodgkin's lymphomas]. / Valor de la gammagrafía con 99mTc-MIBI en el diagnóstico y seguimiento de los linfomas Hodgkin y no Hodgkin.

UNLABELLED: This work aimed to assess the utility of 99mTc-MIBI scintigraphy in the diagnosis and follow-up of lymphoma patients. Seventy-two patients with a previous diagnosis of lymphoma (41 with Hodgkin's and 31 with non-Hodgkin's disease) and a control group of 8 patients with palpable lymph nodes and a negative diagnosis of lymphoma based on the clinical examination, chest x-ray, lymphography, ultrasounds and biopsy were studied. Whole body scintigraphies were performed 20 min and 2 h after i.v. administration of 740 MBq of 99mTc-MIBI. The joint result of the already mentioned standard diagnostic tests was considered as the confirmation criterion. A sensitivity, specificity and accuracy of 96,2%, 100% and 97,4% respectively were obtained. Kappa coefficient was k = 0,94 +/- 0,11. CONCLUSION: Scintigraphy with 99mTc-MIBI is a useful tool for the diagnosis and follow-up of lymphomas regardless of their classification.

Valor de la gammagrafía con 99mTc-MIBI en el diagnóstico y seguimiento de los linfomas Hodgkin y no Hodgkin / Value of the scintigraphy with 99mTc-MIBI in the diagnosis and follow-up of Hodgkin's and Non-Hodgkin's lymphomas

El objetivo del presente trabajo fue evaluar la utilidad de la gammagrafía con 99mTc-metoxi-isobutil-isonitrilo (MIBI) en el diagnóstico y seguimiento de pacientes que padecen de linfoma. Se estudiaron 72 pacientes con diagnóstico de linfoma (41 Hodgkin y 31 no Hodgkin) y un grupo control de 8 pacientes con ganglios palpables y diagnóstico negativo de linfoma producto de la evaluación clínica, radiografía de tórax, linfografía, ultrasonido y la biopsia. Se realizaron rastreos gammagráficos 20 min y 2 h después de la administración i.v. de 740 MBq de 99mTc-MIBI. El resultado conjunto de los instrumentos diagnósticos antes señalados se tomó como criterio de confirmación. Se obtuvo una sensibilidad, especificidad y exactitud de 96,2 per cent, 100 per cent y 97,4 per cent respectivamente. El coeficiente Kappa fue de 0,94 ñ 0,11. Conclusión: La gammagrafía con 99mTc-MIBI es útil para el diagnóstico y seguimiento de los linfomas, independientemente de su clasificación (AU)

[Myocardial perfusion SPET in the detection of coronary artery disease in orthotopic heart transplantation]. / SPET de perfusión miocárdica en la detección de enfermedad arterial coronaria en el trasplante ortotópico de corazón.

The incidence of atherosclerosis of the heart transplant in long term survivors is 38% at 5 years. In the present work, myocardial perfusion 201Tl-SPET was assessed as a non-invasive diagnostic method for the detection of postransplant coronary artery disease, as well as its efficiency with regard to other techniques. Twenty patients, aged (47 +/- 9) years old, who underwent heart transplantation at least 3 years earlier, were studied by 201Tl-SPET. Qualitative and quantitative analysis of the images were performed. It was found ischemia in 6 patients, 4 of them asymptomatics. In 5 of the 6 positive cases by SPET coronary stenosis was found by angiography. Kappa coefficient and percent of agreement were k = 0. 76 and Pe = 90%, respectively. There were no relationships among rejection crisis, sepsis by cytomegalovirus and coronary artery disease detected by using 201Tl-SPET (p > 0.05). The most relevant risk factors in the sample were hypertension and hyperlipidemia. Two patients died because of coronary artery disease. It was confirmed by necropsy findings. These results suggest that thallium-201 myocardial perfusion tomography could be useful to detect coronary artery disease in the transplanted heart.