RESUMEN
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.
Asunto(s)
Ciclotrones/instrumentación , Radioisótopos de Flúor/aislamiento & purificación , Brasil , Fluorodesoxiglucosa F18/aislamiento & purificación , Semivida , Humanos , Tomografía de Emisión de Positrones , Radiometría/instrumentación , Radiofármacos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Fluorodesoxiglucosa F18/aislamiento & purificación , Técnicas Analíticas Microfluídicas/métodos , Radiofármacos/aislamiento & purificación , Extracción en Fase Sólida/métodos , Fluorodesoxiglucosa F18/química , Técnicas Analíticas Microfluídicas/instrumentación , Radiofármacos/química , Extracción en Fase Sólida/instrumentaciónRESUMEN
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.
Asunto(s)
Ciclotrones , Radioisótopos de Flúor/aislamiento & purificación , Fluorodesoxiglucosa F18/aislamiento & purificación , Radioisótopos/análisis , Ciclotrones/instrumentación , Humanos , Exposición Profesional , Tomografía de Emisión de Positrones , Dosis de Radiación , Residuos Radiactivos/análisis , Generadores de Radionúclidos/instrumentación , Radiofármacos/aislamiento & purificación , Administración de ResiduosRESUMEN
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.
Asunto(s)
Fluorodesoxiglucosa F18/síntesis química , Niobio/química , Platino (Metal)/química , Tantalio/química , Circonio/química , Ciclotrones , Fluorodesoxiglucosa F18/química , Fluorodesoxiglucosa F18/aislamiento & purificación , Microscopía Electrónica de Rastreo , Protones , Titanio , AguaRESUMEN
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.
Asunto(s)
Fluorodesoxiglucosa F18/síntesis química , Radiofármacos/síntesis química , Fluorodesoxiglucosa F18/aislamiento & purificación , Oxígeno/química , Radiofármacos/aislamiento & purificación , Espectrometría gammaRESUMEN
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.
Asunto(s)
Reactores Biológicos , Fluorodesoxiglucosa F18/química , Marcaje Isotópico/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Tomografía de Emisión de Positrones/instrumentación , Radiofármacos/síntesis química , Diseño de Equipo , Análisis de Falla de Equipo , Estudios de Factibilidad , Fluorodesoxiglucosa F18/aislamiento & purificación , Marcaje Isotópico/métodos , Técnicas Analíticas Microfluídicas/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Biotecnología/instrumentación , Fluorodesoxiglucosa F18/química , Marcaje Isotópico/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Tomografía de Emisión de Positrones/instrumentación , Radiofármacos/síntesis química , Biotecnología/métodos , Diseño de Equipo , Análisis de Falla de Equipo , Estudios de Factibilidad , Fluorodesoxiglucosa F18/aislamiento & purificación , Marcaje Isotópico/métodos , Técnicas Analíticas Microfluídicas/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
Cromatografía por Intercambio Iónico/métodos , Fluorodesoxiglucosa F18/síntesis química , Fluorodesoxiglucosa F18/aislamiento & purificación , Marcaje Isotópico/métodos , Iones , Radiofármacos/síntesis química , Radiofármacos/aislamiento & purificación , Soluciones , VolatilizaciónRESUMEN
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.