Micosis fungoide con localización pulmonar detectada con 18F-FDG PET/TC / Mycosis Fungoides Involving the Lungs Detected by 18F-FDG PET/CT

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Testing which is the fitter position sensor for a cyclotron liquid target.

The [(18)F]FDG has 109.7 min half-life, there is a period about 6 h between the beginning of [(18)O]H2O irradiation until the PET-CT exam. Any fail in production chain will result in delay to the PET-CT exam. The absence of the position signs from [(18)O]H2O target valve may result in (18)F production loss. Three types of position sensors were tested. After finding the fitter sensor it was possible to reduce the incidence of fails, increasing the reliability in [(18)F]FDG production chain.

Actualización del uso de radiotrazadores PET en patología inflamatoria / Update on the use of PET radiopharmaceuticals in inflammatory disease

En la actualidad el uso de la imagen molecular con tecnología PET/TC con diferentes radiotrazadores, en especial la 18F-FDG, se está extendiendo más allá del ámbito de la oncología, siendo las enfermedades inflamatorias e infecciosas unas de las que más interés están despertando. En este artículo se hace una revisión de su aplicación y aportación en diferentes patologías inflamatorias en el contexto de las técnicas de imagen estructurales y de medicina nuclear convencional. Se hace especial énfasis en las de mayor entidad como son la vasculitis de grandes vasos, la sarcoidosis, la artritis reumatoide, la enfermedad inflamatoria intestinal y el estudio de la placa de ateroma (AU)

The use of molecular imaging with PET/CT technology using different radiotracers, especially the 18F-FDG is currently spreading beyond the area of oncology, the most interest being placed on inflammatory and infectious diseases. This article presents a review of its contribution in different inflammatory conditions in the context of structural and conventional nuclear medicine imaging. Special emphasis is placed on the more significant diseases such as large-vessel vasculitis, sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of the atheroma plaque (AU)

Utilidad de la tomografía por emisión de positrones con 18F-FDG en un caso de papilomatosis pulmonar recurrente juvenil / Utility of positron emission tomography with 18F-FDG in a case of juvenile recurrent respiratory papillomatosis

La papilomatosis pulmonar recurrente juvenil (PPRJ) es una enfermedad infecciosa que provoca el crecimiento de papilomas en la vía respiratoria en la que hasta en un 4% de los casos degeneran hacia un carcinoma de células escamosas. Presentamos el caso de una paciente de 17 años con PPRJ en la que se valora la utilidad de la 18F-FDG-PET/TC ante la sospecha de malignización de las lesiones papilomatosas. Las técnicas de imagen morfometabólicas, la TC y la PET/TC fueron sugestivas de malignidad. Sin embargo, esta no fue confirmada en el análisis anatomopatológico tras su resección. La FDG-PET/TC no parece una herramienta útil para la detección precoz de malignidad en la PPRJ, aunque sí aumenta la rentabilidad diagnóstica de la biopsia al identificar las lesiones más activas y, por lo tanto, con mayor posibilidad de ser malignas (AU)

Juvenile recurrent respiratory papillomatosis (JRRP) is an infectious disease caused by the growth of papillomas in the airway. Up to 4% of these cases degenerate into squamous cell carcinoma. We present the case of a 17-year-old female patient with JRRP in which the utility of 18F-FDG-PET/CT in the characterization of suspicious papillomatous lesions of malignancy is evaluated. Morphometabolic techniques, CT scan and PET/CT scans were suggestive of malignancy. However, this was not confirmed in the histopathological analysis after its resection. The 18F-FDG-PET/CT does not seem to be a useful tool for early detection of malignancy in JRRP. However, it does increase the diagnostic accuracy of the biopsy as it identifies the most active lesions and, therefore, those most likely to be malignant (AU)

Purification of 2-[18F]fluoro-2-deoxy-d-glucose by on-chip solid-phase extraction.

Microfluidic devices have shown great potential for the production of positron emission tomography (PET) radiotracers, but most devices have focused only on the synthesis step of the procedure, typically neglecting the other important steps such as [(18)F]fluoride pre-concentration and radiotracer purification that could equally benefit from miniaturisation. Here, we demonstrate the development of microfluidic modules for the purification of PET radiotracers, particularly 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG), via the use of on-chip solid-phase extraction (SPE). In these initial tests, the SPE modules were able to yield [(18)F]FDG with up to 90% radiochemical purity, and methods are proposed for further increasing this value.

Analysis of induced radionuclides in replacement parts and liquid wastes in a medical cyclotron solely used for production of 18F for [18F]FDG.

Radioactivities produced in replacement parts and liquid wastes in a medical cyclotron used to produce (18)F for [(18)F]FDG with 10MeV protons were analyzed. Nineteen radionuclides were found in the replacement parts and liquid wastes. Among them, long-lived (56)Co in the Havar foils is critical in terms of radioactive waste management. The estimated dose level of exposure for the operating staff during the replacement of parts was around 310µSv/y, which is smaller than the recommended dose limit for workers.

Assessing the performance and longevity of Nb, Pt, Ta, Ti, Zr, and ZrO2-sputtered Havar foils for the high-power production of reactive [18F]F by proton irradiation of [18O]H2O.

As water-soluble ionic contaminants, which arise following proton irradiation of [18O]H2O have been associated with decreased [18F]FDG yields, the minimization of these contaminants is an asset in improving the [18F]F reactivity. To this end, we have previously demonstrated that the use of Nb-sputtered Havar foils results in decreased radionuclidic and chemical impurities in proton irradiated [18O]H2O, improved [18F]FDG yields, and improved [18F]FDG yield consistency when compared with non-sputtered Havar. Resulting from the highly reactive chemical microenvironment within the target however, this niobium layer is observed to degrade over time. To find a material that displays increased longevity with regards to maintaining high [18F]F reactivity, this project extensively investigated and compared Havar foils sputtered with Nb, Pt, Ta, Ti, Zr and ZrO2. Of the materials investigated, the results of this study suggest that Ta-sputtered Havar foil is the preferred choice. For similar integrated currents (~1,000,000 µA min), when comparing the Ta-sputtered Havar with Nb-sputtered Havar we observed: (i) greater than an order of magnitude decrease in radionuclidic impurities, (ii) a 6.4 percent increase (p=0.0025) in the average TracerLab MX [18F]FDG yield, and (iii) an overall improvement in the FDG yield consistency. Excellent performance of the Ta-sputtered foil was maintained throughout its ~1,500,000 µA min lifetime.

Assessment of radionuclidic impurities in 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) routine production.

In this paper, radionuclidic impurities generated during the bombardment of [18 O]water in the routine production of 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) were studied. In order to assess such impurities and the efficacy of purification methods through the different steps of the synthesis, samples of the target filters, purification columns, [18 O]water recovered after the synthesis, and the final solution was collected and their activities measured and analyzed by means of a gamma-ray spectrometry system. The data demonstrated that purification methods adopted for the synthesis provide the [18F]FDG radionuclidically pure, as requested by the EU Pharmacopeia.

Microfluidic reactor for the radiosynthesis of PET radiotracers.

Here we show the first application of a microfabricated reaction system to PET radiochemistry, we term "microfluidic PET". The short half-life of the positron emitting isotopes and the trace chemical quantities used in radiolabelling make PET radiochemistry amenable to miniaturisation. Microfluidic technologies are capable of controlling and transferring tiny quantities of liquids which allow chemical and biochemical assays to be integrated and carried out on a small scale. Such technologies provide distinct advantages over current methods of PET radiochemical synthesis. To demonstrate "proof of principle" we have investigated the radiohalogenation of small and large molecular weight molecules using the microfluidic device. These reactions involved the direct radioiodination of the apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of 2-[(18)F]FDG from a mannose triflate precursor and fluorine-18 and hence provide a test bed for microfluidic reactions. We demonstrate the rapid radioiodination of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid radiofluorination of 2-[(18)F]FDG (60% radiochemical yield within 4s) using a polymer microreactor chip. Chromatographic analysis showed that the labelling efficiency of the unoptimised microfluidic chip is comparable to conventional PET radiolabelling reactions.

Microfluidic technology for PET radiochemistry.

This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using (18)F and (124)I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [(18)F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4s. The radiolabelling efficiency of (124)I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides.

Rapid synthesis of [18F]FDG without an evaporation step using an ionic liquid.

In this study, we describe a new 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) synthesis without a distillation step. This involves fluorinating in an ionic liquid-containing medium. A test for the effective elution of [18F]fluoride from the anion exchange resin showed the proper selection of the base and the required eluant composition, which is an essential requirement for the automation of [18F]FDG synthesis. An 18F-labeling study by nucleophilic substitution showed that the major factors controlling the yield were the temperature and the reaction medium composition. The 18F-fluorination proceeded with a labeling efficiency of 74.6+/-7.4% (n=8) for optimized conditions. Alkaline hydrolysis and purification carried out in the liquid phase provided a final decay-corrected [18F]FDG yield of 59.1+/-5.1% (n=3), a radiochemical purity of 91.9+/-3.7% (n=3), and a reaction time of 13 min. Alkaline hydrolysis and purification carried out in the solid phase provided a final decay-corrected [18F]FDG yield of 48.8+/-6.0% (n=3), a radiochemical purity of 96.0+/-4% (n=3), and a reaction time of 19 min. The rapid and straightforward synthesis of [18F]FDG can be achieved by eliminating all evaporation steps, which is made possible by the use of ionic liquid-containing media for the fluorination step.

Routine quality control of recycled target [18O]water by capillary electrophoresis and gas chromatography.

Recycling of [(18)O]water for [(18)F]fluoride production can be accomplished with reliable results. We have developed sensitive, robust, and rapid analyses of impurities in [(18)O]water. Anions were quantitated by capillary electrophoresis and organic residuals were quantitated by gas chromatography using methods with excellent reproducibility and linearity. Kryptofix 222 (K-222) was quantitated by a sensitive LC-MS-MS technique. Isotopic composition was determined by GC-MS with satisfactory accuracy and precision. These methods were employed to evaluate recovered [(18)O]water purified by a novel electrolysis method. 2-[(18)F]FDG yields using purified [(18)O]water with very low levels of impurities are indistinguishable from newly purchased [(18)O]water. High (> 300 ppm) carbonate concentration reduces the fluoride trapping efficiency of QMA. The analyses of anions, organics, and isotopic enrichment were applied routinely for quality control of [(18)O]water to predict a satisfactory outcome of 2-[(18)F]FDG production.