Strategies for PET imaging of the receptor for advanced glycation endproducts (RAGE) / 药物分析学报

The implication of the receptor for advanced glycation end-products (RAGE) in numerous diseases and neurodegenerative disorders makes it interesting both as a therapeutic target and as an inflammatory biomarker. In the context of investigating RAGE as a biomarker, there is interest in developing radio-tracers that will enable quantification of RAGE using positron emission tomography (PET) imaging. We have synthesized potential small molecule radiotracers for both the intracellular ([18F]InRAGER) and extracellular ([18F]RAGER) domains of RAGE. Herein we report preclinical evaluation of both using in vitro (lead panel screens) and in vivo (rodent and nonhuman primate PET imaging) methods. Both radiotracers have high affinity for RAGE and show good brain uptake, but suffer from off-target binding. The source of the off-target PET signal is not attributable to binding to melatonin receptors, but remains unexplained. We have also investigated use of lipopolysaccharide (LPS)-treated mice as a possible animal model with upregulated RAGE for evaluation of new imaging agents. Immunoreactivity of the mouse brain sections revealed increases in RAGE in the male cohorts, but no difference in the female groups. However, it proves challenging to quantify the changes in RAGE due to off-target binding of the radio-tracers. Nevertheless, they are appropriate lead scaffolds for future development of 2nd generation RAGE PET radiotracers because of their high affinity for the receptor and good CNS penetration.

La formación de profesionales nucleares y su contribución al desarrollo de La Habana / The training of nuclear professionals and their contribution to the development of Havana

RESUMEN El presente trabajo muestra el desarrollo que ha tenido la formación de profesionales nucleares en Cuba durante más de treinta y ocho años. Se exponen las características principales de los programas de estudio de las carreras nucleares acreditadas por el sistema nacional de acreditación de la educación superior cubana. Algunos indicadores de la calidad de la formación en ingeniería nuclear, física nuclear y radioquímica, la presencia de la mujer, así como, la contribución de estas carreras al desarrollo de la provincia La Habana a partir de un análisis de la ubicación de sus egresados son presentados.

ABSTRACT This work shows the development that has taken the education of nuclear professionals in Cuba for more than thirty-eight years. The main features of the curriculum for undergraduate specialty for nuclear matters, accredited by the national accreditation system of higher education in Cuba are introduced. Some quality indicators, the women presence and the contribution of the nuclear careers to the development of Havana province beginning from the analysis of graduated distribution in the labor market are discussed.

Evaluación isotópica del fósforo de un suelo ferralítico rojo bajo varios sistemas de fertilización / Phosphorus isotopic evaluation of a Red Ferralitic soil under various fertilization systems

Se analizaron muestras de un suelo ferralítico rojo de la Estación Experimental “Juan Tomás Roig” de la Universidad de Ciego de Ávila, sometido a dos rotaciones de cultivo y cuatro sistemas de fertilización fosfórica. El objetivo fue evaluar, mediante la dilución isotópica del 32P, los parámetros estáticos del fósforo (P) en un suelo que recibió fertilizante fosfórico por dos métodos de aplicación (en bandas y a voleo) durante varios años. Se utilizó un método radioquímico de laboratorio usando una disolución marcada con 32P libre de portador, basado en el intercambio isotópico entre los fosfatos de los sólidos y la solución del suelo. Las muestras de suelo se analizaron en los laboratorios del Departamento del Comisariado de Energía Atómica, Francia. Se determinaron los factores cantidad (E1) como el P isotópicamente intercambiable en un minuto, intensidad (Cp) como la concentración de P en la solución del suelo y capacidad como la relación E1/Cp. La evaluación isotópica mediante 32P indicó que el suelo necesita de aplicaciones de P altas y en bandas para alcanzar valores de E1 y Cp adecuados para la nutrición de los cultivos agrícolas. Con la fertilización en bandas se logró un efecto acumulativo del P en el suelo después de tres ciclos de rotación de cultivos, que permitió incrementar su disponibilidad para las plantas. El factor capacidad resultó muy alto en todas las muestras de suelo, lo cual indica que el suelo mantiene una reserva de P que es difícilmente intercambiable con el P de la solución del suelo

Soil samples from a red ferralitic soil from the "Juan Tomás Roig" Experimental Station, belonging to Ciego de Avila University were analyzed under two crop rotations and four phosphoric fertilization systems. The objective was to evaluate, through the 32P isotopic dilution, phosphor (P) static parameters in a soil that has received P fertilizer through two placement methods (banding and broadcasting) for several years. A radiochemical laboratory method using a 32P free-carrier solution as a tracer based on isotopic exchange between solid phase and soil solution phosphate ions was used. Soil samples were analyzed at the CEA Department laboratories, in Francia. Quantity (E1), as isotopic exchangeable P at one minute, intensity (Cp), as P concentration in soil solution, and capacity, as (E1/Cp), factors were determined. 32P isotopic evaluation indicated that the soil needs high banding P application to reach adequate E1 and Cp values for crop nutrition. A cumulative P effect in the soil through banding fertilization after three crop rotation cycles was obtained, which allows to increase plant P availability. The capacity factor was very high in all soil samples, indicating that soil maintains a P reserve that is difficult to exchange with the phosphor present in the soil solution

Research on multifunctional 18F synthesis module with two vessels / 中华核医学杂志

Objective To explore a new 18F multifunctional synthesis module with two vessels to synthesize various kinds of 18F labeled radiopharmaceuticals for clinical utilities. Methods The module with two vessels contained five systems, capture of F ion, the first reaction vessel, the second reaction vessel, high performance liquid chromatography (HPLC) purification, and solid extraction. The two vessels were made of transparent glass and were used to prepare complex products by nucleophilic reaction or hydrolyzation. Results The complex compounds of 18F-ethyl-choline, 18F-N-succinimidyl-4-18 F-fluorobenzoate (SFB), and common compounds of 18F-fluorodeoxyglucose (FDG), 18F-3'-deoxy-3'-18 F-fluorothymidine (FLT) were synthesized by the new module. The uncorrected synthesis yield (EOS) of 18F-SFB, 18F-ethylcholine, and 18F-FDG were (28.2±1.9)% (n=5), (22.5±3.8)%(n=6), and (58.2±5.4)% (n=32), respectively. The corrected synthesis yield of 18F-FLT was (30.1 ±6.2)% ( n = 10). In addition,11C-N-methyl-N-( 1-methylpropyl )-1-( 2-corophenyl )-isoquinoline-3 -carboxamide ( PK11195 ) was also prepared by the module with the yield of (31.2 ± 2.5) % ( n = 3 ). Conclusions The new module with two vessels has been used for synthesis of many 18F compounds and it may have the potential to be used for other more 18F radiopharmaceuticals.