Browsing by Author "Salvadori, PA"
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- ItemDesign, synthesis and preliminary evaluation of 18F-labelled 1,8-naphthyridin- and quinolin-2-one-3-carboxamide derivatives for PET imaging of CB2 cannabinoid receptor(Elsevier, 2015-06-15) Saccomanni, G; Pascali, G; Del Carlo, S; Panetta, D; De Simone, M; Bertini, S; Burchielli, S; Digiacomo, M; Macchia, M; Manera, C; Salvadori, PAIn the present work, we report the synthesis of new aryliodonium salts used as precursors of single-stage nucleophilic 18F radiofluorination. The corresponding unlabelled fluorinated derivatives showed to be CB2 cannabinoid receptor specific ligands, with Ki values in the low nanomolar range and high CB2/CB1 selectivity. The radiolabelled compound [18F]CB91, was successfully formulated for in vivo administration, and its preliminary biodistribution was assessed with microPET/CT. This tracer presented a reasonable in vivo stability and a preferential extraction in the tissues that constitutionally express CB2 cannabinoid receptor. The results obtained indicate [18F]CB91 as a possible candidate marker of CB2 cannabinoid receptor distribution. This study would open the way to further validation of this tracer for assessing pathologies for which the expression of this receptor is modified. © 2015 by Elsevier Ltd.
- ItemHardware and software modifications on the Advion NanoTek microfluidic platform to extend flexibility for radiochemical synthesis(Elsevier Ltd., 2014-02) Pascali, G; Berton, A; DeSimone, M; Wyatt, NA; Matesic, L; Greguric, ID; Salvadori, PAMicrofluidic systems are currently receiving a lot of attention in the PET radiochemistry field, due to their demonstrated ability to obtain higher incorporation yields with reduced total processing time and using a decreased amount of precursors. The Advion NanoTek LF was the first commercial microfluidic system available for radiochemistry that allows basic parameter optimization to be performed. In this paper we report hardware and software modifications that would allow better performing procedures, higher product throughput and flexibility to utilize the system. In particular, HPLC purification and SPE formulation have been fully integrated. © 2014 Elsevier Ltd.
- ItemIdentification of chemical byproducts in the radiofluorination of structurally complex aryliodonium salts(Springer Nature, 2014-08-24) Pascali, G; Del Carlo, S; Rocchiccioli, S; Signore, G; Saccomanni, G; Manera, C; Macchia, M; Salvadori, PAThe use of direct radiofluorination of aryliodonium salts represents a promising route to new PET tracers. This study tested the use of these precursors for obtaining candidate ligands of the cannabinoid type-2 receptor. 18F-labelling was performed using microfluidic technology, which allowed obtaining good incorporation yields. A closer inspection of the chemical composition of the reaction mixture evidenced the recurrent occurrence of chemical byproducts (H-adduct) due to a reductive side reaction of these substrates. The H-adduct formation seems to be unrelated to water presence, needed for obtaining a satisfactory incorporation, and may become an important feature for assessing the real-life accessibility of new radiotracers through the use of aryliodonium precursors. © 2014 Akadémiai Kiadó, Budapest, Hungary
- ItemMicrofluidics in radiopharmaceutical chemistry(Elsevier B.V., 2013-08-01) Pascali, G; Watts, P; Salvadori, PAThe increased demand for molecular imaging tracers useful in assessing and monitoring diseases has stimulated research towards more efficient and flexible radiosynthetic routes, including newer technologies. The traditional vessel-based approach suffers from limitations concerning flexibility, reagent mass needed, hardware requirements, large number of connections and valves, repetitive cleaning procedures and overall big footprint to be shielded from radiation. For these reasons, several research groups have started to investigate the application of the fast growing field of microfluidic chemistry to radiosynthetic procedures. After the first report in 2004, many scientific papers have been published and demonstrated the potential for increased process yields, reduced reagent use, improved flexibility and general ease of setup. This review will address definitions occurring in microfluidics as well as analyze the different approaches under two macro-categories: microvessel and microchannel. In this perspective, several works will be collected, involving the use of positron emitting species (11C, 18F, 64Cu) and the fewer examples of gamma emitting radionuclides (99mTc, 125/131I). New directions in microfluidic research applied to PET radiochemistry, future developments and challenges are also discussed. © 2013 Elsevier Inc.
- ItemOptimization of nucleophilic 18F radiofluorinations using a microfluidic reaction approach(Nature Publishing Group, 2014-07-31) Pascali, G; Matesic, L; Collier, TL; Wyatt, NA; Fraser, BH; Pham, TQ; Salvadori, PA; Gueguric, IMicrofluidic techniques are increasingly being used to synthesize positron-emitting radiopharmaceuticals. Several reports demonstrate higher incorporation yields, with shorter reaction times and reduced amounts of reagents compared with traditional vessel-based techniques. Microfluidic techniques, therefore, have tremendous potential for allowing rapid and cost-effective optimization of new radiotracers. This protocol describes the implementation of a suitable microfluidic process to optimize classical 18F radiofluorination reactions by rationalizing the time and reagents used. Reaction optimization varies depending on the systems used, and it typically involves 5–10 experimental days of up to 4 h of sample collection and analysis. In particular, the protocol allows optimization of the key fluidic parameters in the first tier of experiments: reaction temperature, residence time and reagent ratio. Other parameters, such as solvent, activating agent and precursor concentration need to be stated before the experimental runs. Once the optimal set of parameters is found, repeatability and scalability are also tested in the second tier of experiments. This protocol allows the standardization of a microfluidic methodology that could be applied in any radiochemistry laboratory, in order to enable rapid and efficient radiosynthesis of new and existing [18F]-radiotracers. Here we show how this method can be applied to the radiofluorination optimization of [18F]-MEL050, a melanoma tumor imaging agent. This approach, if integrated into a good manufacturing practice (GMP) framework, could result in the reduction of materials and the time required to bring new radiotracers toward preclinical and clinical applications. © 2014, Nature Publishing Group
- ItemPurification of 2-[18F]fluoro-2-deoxy-d-glucose by on-chip solid-phase extraction(Elsevier B.V., 2013-03-08) Tarn, MD; Pascali, G; De Leonardis, F; Watts, P; Salvadori, PA; Pamme, NMicrofluidic 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 [18F]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-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG), via the use of on-chip solid-phase extraction (SPE). In these initial tests, the SPE modules were able to yield [18F]FDG with up to 90% radiochemical purity, and methods are proposed for further increasing this value. © 2013 Elsevier B.V.
- ItemRadiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals(The Royal Society of Chemistry, 2013-03-25) Arima, V; Pascali, G; Lade, O; Kretschmer, HR; Bernsdorf, I; Hammond, V; Watts, P; De Leonardis, F; Tarn, MD; Pamme, N; Cvetkovic, BJ; Ditrrich, PS; Vasovic, N; Duane, R; Jaksic, A; Zacheo, A; Zizzari, A; Marra, L; Perrone, E; Salvadori, PA; Rinaldi, RAbstractWe have developed an integrated microfluidic platform for producing 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in continuous flow from a single bolus of radioactive isotope solution, with constant product yields achieved throughout the operation that were comparable to those reported for commercially available vessel-based synthesisers (40–80%). The system would allow researchers to obtain radiopharmaceuticals in a dose-on-demand setting within a few minutes. The flexible architecture of the platform, based on a modular design, can potentially be applied to the synthesis of other radiotracers that require a two-step synthetic approach, and may be adaptable to more complex synthetic routes by implementing additional modules. It can therefore be employed for standard synthesis protocols as well as for research and development of new radiopharmaceuticals. © 2013 The Royal Society of Chemistry
- ItemRadiopharmacy and radiopharmaceuticals: 2007 update(Edizioni Minerva Medica, 2007-03) Zavitsanou, K; Nguyen, VH; Salvadori, PA; Salvadori, P; Smith, SVThis issue contains research papers of selected highlights from the 13th European Symposium of Radiopharmacy and Radiopharmaceuticals, held in Lucca, Italy on 30 March-2 April 2006.
- ItemTolerance of water in microfluidic radiofluorinations: a potential methodological shift?(Akadémiai Kiadó, 2014-07-1) Pascali, G; De Simone, M; Matesic, L; Greguric, ID; Salvadori, PANucleophilic [18F]-fluorination reactions traditionally include a drying step of the labeling agent in order to achieve a successful substitution. This passage extends the time and complexity required for the whole radiotracer production, with increased hardware and detrimental effects on the radioactive recovery of such a short-lived (t½=109 min) isotope. Because the performance of radiofluorination reactions conducted under microfluidic flow conditions have been demonstrated to be more effective in terms of reaction time and yields, we have tested the tolerance to water present in this specific reaction condition, in view of eliminating the drying step in the process. To this purpose, we tested different substrates selected from typical radiofluorination intermediates. Our results show that water could be tolerated in a microfluidic environment; in particular, we observed a slight decrease in the labeling of aromatic precursors and a significant increase for iodonium salts, whereas the radiochemical yields of the other compounds studied were virtually unchanged. These findings may open the way to the possibility of simpler and faster processes for the production of new 18F-fluorinated positron emission tomography tracers. © 2014 Akadémiai Kiadó