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The work provides arguments for the selection of 18 MeV cyclotron in protons, in its Twin variant. It will be used only for nuclear reactions with these particles in order to ensure the supply of radionuclides in Cuba, for the positron emission tomography (18F mainly) as well as for single photon emission computed tomography (123I, for example), in the future. Data indicating the possibility of supplying 18F-FDG to at least five PET centers are given. This shall allow Cuba to access the one of the most advanced imaging technology, with the consequent benefit for patients suffering from cancer, cardiovascular and neurological diseases. [ABSTRACT FROM AUTHOR]

The positron emission tomography is a technique of medical image of great sensibility and high resolution that requires short-lived positron emitting radionuclides. The most commonly used are 18F and 11C. The main difficulty of these radionuclides is the necessity to install a cyclotron in the site of use or not very far from it. Therefore convenient radionuclides have been researches, among them 68Ga. The availability of this radionuclide from long-lived 68Ge/68Ga generators, which can been used for along time far from the cyclotron location, and the rich coordination chemistry of Ga3+ have allowed to incorporate to the medical practice some radiopharmaceuticals as well as the research of a variety of stables complexes of Ga3+ coupled to biomolecules for diagnostic imaging of cancer and cardiovascular and neurological diseases. The present work is aimed at examining the potentialities of the 68Ga-radiopharmacy. [ABSTRACT FROM AUTHOR]

En su conferencia Nobel en 1908, Paul Ehrlich destaca la importancia del descubrimiento de la célula como resultado de la invención del microscopio y lo que trajo aparejado para entender el fenómeno de la vida. Indicó las limitaciones metódicas de ese tipo de instrumentos, vislumbró el alcance mayor del objeto de estudio: "…Me inclino a pensar -dijo- que estamos cercanos al límite de lo que el microscopio ha hecho y podía hacer por nosotros y que para la profundización ulterior en el importante problema de la vida celular, que todo lo gobierna, serían inútiles los más refinados dispositivos ópticos. Ahora ha llegado el momento de penetrar en el más sutil quimismo de la vida celular, de desdoblar el concepto de la célula como unidad en un gran número de funciones parciales específicas" [1]. [ABSTRACT FROM AUTHOR]

The results obtained in the last ten years by the institutions of the Executive Secretariat for Nuclear Affairs (SEAN) in the field of radiochemistry and analitical nuclear techniques to answer for the increase and development of applications in radioisotopes in the different branches of science and economy are given in this paper. The link between the works made and the creation of the infrastructure needed for applications, as well as with the solution to the problems arisen from practice is shown. Perspectives for radiochemistry development in its more applied branch and for analitical nuclear techniques as a part of the analitical basis SEAN has, are examined. [ABSTRACT FROM AUTHOR]

The international radiopharmaceutical market is considered as a reference to characterize the cuban scenario. The demand for diagnostic and therapeutic radiopharmaceuticals increases in the world around 10% each year. An indicator of this increase in the diagnostic area is the number of gamma cameras per million inhabitants: 20 in developed countries and 0,8 in developing countries, on average. In the Latin American region the average is 2,6. In Cuba this indicator has grown from 1.24 in 2013 to 1.78 at present and should reach 2.57 in 2020, including the PET-CT currently under installation. In order to contribute to a more efficient use of these techniques, new radiopharmaceuticals, based on 99mTc for the diagnosis of diseases of the central nervous system, infections and some types of cancer, will be introduced in the diagnostic area in the short term. In the therapeutic area, the growth of radiopharmaceutical market for the treatment of thyroid diseases, metastatic bone pain, non-Hodgkin's lymphoma and neuroendocrine tumors, is expected. Itrium-90 [90Y] is considered one of the radionuclides with a great perspective in this field. All the above mentioned favors the fact that nuclear medicine procedures are incorporated into routine health-care systems, as already occurred in developed countries. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumors specifically over-express somatostatin receptors. Their diagnosis has expanded due to radiolabelling of DOTA-peptides such as somatostatin analogue DOTA-1-Nal3-Octreotide (DOTA-NOC) conjugated to β+ emitting radionuclides such as 68Ga, with very favorable decay-properties. This paper describes the radiolabeling procedures of DOTA-NOC with 68Ga, in a pure aqueous medium and in presence of non-aqueous solvents as well as the methods used for quality control where a formulation is obtained with a radiochemical yield exceeding 95%. Adding ethanol (30% - v / v) to the reaction mixture allowed increasing the specific activity of 68Ga-DOTA-NOC radioconjugated, reaching a value of 182 MBq / nmol, higher than reported in literature (50 MBq / nmol) for labeling in a pure aqueous medium. Stability studies are also presented (in presence of saline solution and saline phosphate buffer, transmetallation studies in Fe3+, Ca2+, Mg2+ and Zn2+ solutions, challenges competition against EDTA and DTPA chelators and in vitro stability in human transferrin) performed to 68Ga-DOTA-NOC radioconjugated, showing its high stability (> 95%). Compared with the aqueous medium, the use of non aqueous solvents in the synthesis of radioconjugate DOTA-1-Nal3-octreotide labeled with gallium-68, helps reduce the mass of conjugate and the reaction time, significantly increase yields and specific activity of the labeled compound. This could facilitate obtaining the product with better characteristics in modular systems that are under development. [ABSTRACT FROM AUTHOR]

The high morbidity and mortality of cancer makes this condition a serious health problem both in Cuba and other countries. Radioimmunodiagnosis and radioimmunotherapy based in the growing biotechnological advances, and the present knowledge of molecular and cellular biology, become highly promising tools in the fi ght against cancer. This paper presents a brief review of radiopharmaceuticals produced in Cuba from biomolecules, as well as an overview of several monoclonal antibodies and radionuclides used in clinical applications. Radioimmunodiagnosis applications are based on murine monoclonal antibodies, produced in form of lyophilized kits for 99mTc labeling. We also study the outlook for the application of radioimmunotherapy in Cuba from the international experiences, particularly in non-Hodgkin's lymphoma treatment, considering the availability of different monoclonal antibodies already humanized, as well as 90Y, from the existing technologies in Cuban research-production centers [ABSTRACT FROM AUTHOR]

The quality criteria of radioactive dispersions used in radiosynovectomy are examined, taking into account the requirements of the Pharmacopoeia for the Chromic Phosphate P-32 of Mallinckrodt, recommendations for the use of approved radiopharmaceuticals of the European Association of Nuclear Medicine and data provided by others marketing firms. The behavior of two formulations of chromic phosphate, one 32P-labeled and the second 90Y-labeled, from the point of view of the consistency (reproducibility) of both the radiochemical purity and the particle size distribution was assayed. It is proven that the presence of 5% of free phosphate admitted in the Mallinckrodt formulation, and extended to the presence of ionic forms of other radiopharmaceuticals of different matrices, is probably due to the inevitable effect of steam sterilization on the suspension. Based on these results and the accumulated clinical experience, it is considered that to establish the quality requirements of the radioactive suspensions for radiosynovectomy, more attention should be paid to the particle size distribution than to the percentage of free ionic forms. The first one is more related to the efficacy and safety of this kind of radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

In this paper the prevalence of metastatic bone pain is estimated in our country in no less than 3 750 patients. Moreover, the role of 32P-phosphate, which effectiveness is comparable to other radiopharmaceuticals, and the possible return to its previous general use, as it is cheaper, is examined. The fact that 32P is considered more radiotoxic doesn’t invalidate it as a treatment option, which is also evidenced by the Cuban experience. The Center of Isotopes (Centis) has established a production line of up to 37 GBq (1 Ci) per week of high quality 90Y. The fact of its being obtained through a radionuclide generator by electrochemical separation from 90Sr makes the import of radioactive raw material practically not required for indefinite time. This implies that the radionuclide could be available in a sustainable way. By having the 90Y greater β- emission energy, it might be more radiotoxic than 32P. Nevertheless, some evidences show that 32P in the form of orthophosphate is more radiotoxic than 90Y citrate. In Europe, a radiopharmaceutical consisting of a lyophilized kit of EDTMP and 90Y Chloride solution was able to relief pain in 191 patients. Centis has registered the 900Y chloride solution for labeling. Then the task is to introduce in the market a radiopharmaceutical with this radioactive precursor and the imported lyophilized kit in order to increase the treatment to an important number of patients that, as a result, could be benefitted. [ABSTRACT FROM AUTHOR]

La sinovitis crónica, complicación frecuente en artritis reumatoide y hemofilia, es tratada con éxito mediante inyecciones intrarticulares de dispersiones radiactivas (radiosinoviortesis). En Cuba está en uso una formulación de fosfato crómico marcado con 32P. A fi n de aumentar el escalado, perfeccionar la tecnología y obtener formulaciones con otros radionúclidos, se estudia la reacción de obtención del precipitado, basada en la reducción de Cr(VI) a Cr(III) con iones sulfi to en presencia de iones fosfato. Si la relación Na2SO3/CrO3 es 18.5 veces, la precipitación tiene lugar próximo a las dos horas a temperatura ambiente y el pH crece al inicio y permanece luego constante a 7.63 por acción buffer del sulfi to. Se estableció que la reducción de Cr(VI) a Cr(III) a ese pH sigue una reacción de segundo orden. La formación de especies insolubles de cromo y fósforo favorece la reducción. A 70 °C la precipitación ocurre de inmediato. Por el método de los indicadores radiactivos se establece que la relación Cr/P = 1.6 en el precipitado, tanto a temperatura ambiente como a 70 °C. En este caso, cada componente de la razón y la masa disminuyen en un 8%, lo que indica probablemente se trate de un solo producto. El calor acelera la formación del precipitado y lo disuelve en parte. Si Na2SO3/CrO3 = 1.5, el precipitado se forma de inmediato a temperatura ambiente alrededor de pH 5. Bajo las condiciones utilizadas, las especies de cromo en el precipitado aumentan con el pH. Se sugieren posibles composiciones para los productos obtenidos. Chronic sinovitis, a frequent complication in rheumatoid arthritis and hemophilia, is successfully treated by means of intrarticular injections of radioactive dispersions (radiosynoviorthesis). In Cuba, a formulation of chromic phosphate labeled with 32P is used. In order to scale up the process, improve the technology and obtain formulations with other radionuclides, the reaction, based on the reduction of Cr(VI) to Cr(III) with sulphite ions in presence of ions phosphate is studied. If the relationship Na2SO3/ CrO3 is 18.5 times, the precipitation takes place at room temperature roughly at two hours and the pH increases at the beginning and then remains constant at 7.63 because of the buffer action of the sulphite. It was established that the reduction of Cr(VI) to Cr(III) at this pH is a second order reaction. The formation of insoluble species of chromium and phosphor, favors the reduction. At 70 °C the precipitation occurs immediately. Using the method of radioactive indicators, it was established that the relationship Cr/P in the precipitate, at room temperature and at 70 °C is 1.6. In this case, each component of the relationship and the mass diminish in 8%, which indicates we are probably in presence of the same product. The heat accelerates the formation of the precipitate and partially dissolves it. If Na2SO3/CrO3 = 1.5, and the pH value around 5, the precipitate is formed immediately at room temperature. Under the used experimental conditions, the chromium species in the precipitate increase as the pH increases. Possible compositions for the obtained products are suggested. [ABSTRACT FROM AUTHOR]

The paper reviews the current status of the use of radiopharmaceuticals in the treatment of pain caused by bone metastases putting emphasis on the doses used, the effectiveness and safety of developing and on-the-market products. The convenience of the routine use in the case of multiple metastasis is established, since the results are adequate and the risks acceptable. The doses and the adverse effects are considered. The importance of the costs is given, as well as the availability of radionuclides. Reference is made to both the practice in developed countries and those with limited resources. The Cuban experience and the perspectives of the use in our country are pointed out [ABSTRACT FROM AUTHOR]

Phagocytosis in vivo and in vitro of a suspension of chromic phosphate (III) labeled with 51Cr and 32P is studied. The radioactive particles dispersed in a media of 2% gelatin in acetate buffer pH 4-4.5 have a predominant size of 0.8 µm and 5 µm. According with biodistribution experiments in rats after 30 minutes near the 80% of radioactivity is registered in the liver, probably associated with phagocytosis of the particles by liver Kupffer cells. Is also showed that the suspension particles are phagocytized in vitro by mouse peritoneal macrophages. This facts indicate that the studied suspension have appropriate characteristics to be used in radiosynoviorthesis according to the principal action mechanism described for this procedure, particles phagocytosis by cells present in the inflamed synovium. [ABSTRACT FROM AUTHOR]