Browsing by Author "Pascali, G"

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    [18F]Ethenesulfonyl fluoride as a practical radiofluoride relay reagent
    (John Wiley & Sons, Inc, 2019-04-11) Zhang, B; Fraser, BH; Klenner, MA; Chen, Z; Liang, SH; Massi, M; Robinson, AJ; Pascali, G
    Fluorine-18 is the most utilized radioisotope in positron emission tomography (PET), but the wide application of fluorine-18 radiopharmaceuticals is hindered by its challenging labelling conditions. As such, many potentially important radiotracers remain underutilized. Herein, we describe the use of [18F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres. [18F]ESF has a simple and reliable production route and can be stored on inert cartridges. The cartridges can then be shipped remotely and the trapped [18F]ESF can be liberated by simple solvent elution. We have tested 18 radiolabelling precursors, inclusive of model and clinically used structures, and most precursors have demonstrated comparable radiofluorination efficiencies to those obtained using a conventionally dried [18F]fluoride source. © 2019 Wiley-VCH Verlag GmbH & Co.
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    [18F]Fluorination optimisation and the fully automated production of [18F]MEL050 using a microfluidic system
    (CSIRO Publishing, 2014-06-06) Matesic, L; Kallinen, A; Wyatt, NA; Pham, TQ; Greguric, I; Pascali, G
    The [18F]radiolabelling of the melanin-targeting positron-emission tomography radiotracer [18F]MEL050 was rapidly optimised using a commercial continuous-flow microfluidic system. The optimal [18F]fluorination incorporation conditions were then translated to production-scale experiments (35–150 GBq) suitable for preclinical imaging, complete with automated HPLC–solid phase extraction purification and formulation. [18F]MEL050 was obtained in 43 ± 10 % radiochemical yield in ~50 min. © 2015 CSIRO Publishing.
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    Design, 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, PA
    In 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.
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    Effect of rhenium(i) complexation on aza-Michael additions to 5-amino-1,10-phenanthroline with [18F]ethenesulfonyl fluoride towards PET optical tracer development
    (CSIRO Publishing, 2019-01-14) Klenner, MA; Pascali, G; Zhang, B; Ciancaleoni, G; Massi, M; Fraser, BH
    Conjugations with the recently developed [18F]ethenesulfonyl fluoride ([18F]ESF) were performed on 5-amino-1,10-phenanthroline, in its free form and coordinated to a rhenium(i) tricarbonyl complex, as a means of radiosynthesizing dual-modal optical and positron emission tomography (PET) tracers. The Michael-donating ability of the aromatic amine was noticeably perturbed on coordination with the rhenium(i) centre, resulting in decreased radiochemical yields from 34 %, in the case of the free ligand, to 1 %. We attribute the decreased nucleophilicity of the amine to metal deactivation from the electron-withdrawing feature of the rhenium(i) tricarbonyl centre, based on spectroscopic and computational evidence, thus highlighting this effect as a crucial parameter in designing late-stage metal coordination methods employing related aza-Michael additions. Photophysical analyses were also performed on the ESF-conjugated rhenium(i) complex, exhibiting a longer decay lifetime from the triplet metal-to-ligand charge transfer excited state when compared with the non-conjugated analogue. © CSIRO 1996-2021
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    Elemental contamination of an open-pit mining area in the Peruvian Andes
    (Springer Link, 2014-01-21) Bianchini, F; Pascali, G; Campo, A; Orecchio, S; Bonsignore, R; Blandino, P; Pietrini, P
    New technologies and higher prices of raw materials have promoted the expansion of mining activity throughout the world; if not properly regulated, this activity can lead to contamination of the local and regional environment. The city of Cerro de Pasco is located close to a large open-pit mine and in recent years, several reports have provided evidence of environmental contamination and related health problems. The aim of this paper is to evaluate the contamination in fluvial water, sediments and biological fluids from this area. The collective results show elevated metal and metalloid concentrations in rivers and sediments, especially in the areas downstream of the mine. For instance, Pb concentration in rivers downstream of the mine was 4.451 mg/L, while it was 0.037 mg/L upstream of the mine. Sediments also show higher concentration of metals and metalloids in the areas under the influence of the mine. Concentrations of elements in human blood were measured in the population of Paragsha, a village close to the mine. Analysis of the blood samples revealed elevated levels of metals and metalloids, particularly Pb, Cr, Al, Ni and Mn. All of the studied population showed blood concentrations of Al, Cr and Ni higher than those recommended by the WHO. The high concentration of elements found in the blood of the population could be related to the high concentration in the surrounding water sources, but further studies are required to determine the exact sources of exposure to these metals and metalloids. © 2014, Islamic Azad University (IAU).
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    A fluorine-18 radiolabeling method enabled by rhenium(I) complexation circumvents the requirement of anhydrous conditions
    (John Wiley & Sons, Inc, 2017-03-22) Klenner, MA; Pascali, G; Zhang, B; Sia, TR; Spare, LK; Krause-Heuer, AM; Aldrich-Wright, JR; Greguric, I; Guastella, AJ; Massi, M; Fraser, BH
    Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes. © 2017 John Wiley & Sons, Inc
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    Hardware 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, I; Salvadori, PA
    Microfluidic 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.
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    Identification 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, PA
    The 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
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    Kinetic isotope effects and synthetic strategies for deuterated carbon-11 and fluorine-18 labelled PET radiopharmaceuticals
    (Elsevier, 2021-04-16) Klenner, MA; Pascali, G; Fraser, BH; Darwish, TA
    The deuterium labelling of pharmaceuticals is a useful strategy for altering pharmacokinetic properties, particularly for improving metabolic resistance. The pharmacological effects of such metabolites are often assumed to be negligible during standard drug discovery and are factored in later at the clinical phases of development, where the risks and benefits of the treatment and side-effects can be wholly assessed. This paradigm does not translate to the discovery of radiopharmaceuticals, however, as the confounding effects of radiometabolites can inevitably show in preliminary positron emission tomography (PET) scans and thus complicate interpretation. Consequently, the formation of radiometabolites is crucial to take into consideration, compared to non-radioactive metabolites, and the application of deuterium labelling is a particularly attractive approach to minimise radiometabolite formation. Herein, we provide a comprehensive overview of the deuterated carbon-11 and fluorine-18 radiopharmaceuticals employed in PET imaging experiments. Specifically, we explore six categories of deuterated radiopharmaceuticals used to investigate the activities of monoamine oxygenase (MAO), choline, translocator protein (TSPO), vesicular monoamine transporter 2 (VMAT2), neurotransmission and the diagnosis of Alzheimer's disease; from which we derive four prominent deuteration strategies giving rise to a kinetic isotope effect (KIE) for reducing the rate of metabolism. Synthetic approaches for over thirty of these deuterated radiopharmaceuticals are discussed from the perspective of deuterium and radioisotope incorporation, alongside an evaluation of the deuterium labelling and radiolabelling efficacies across these independent studies. Clinical and manufacturing implications are also discussed to provide a more comprehensive overview of how deuterated radiopharmaceuticals may be introduced to routine practice. © 2021 Published by Elsevier Inc.
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    Labeled rhenium complexes: radiofluorination, α-MSH cyclization, and deuterium substitutions
    (American Chemical Society, 2020-06-19) Klenner, MA; Darwish, TA; Fraser, BH; Massi, M; Pascali, G
    While radiopharmaceuticals incorporating rhenium-188 or rhenium-186 radioisotopes have been well documented in the literature, the labeling of rhenium complexes with alternative isotopes has received comparatively less attention. Such rhenium complexes have demonstrated significant utility in imaging melanoma tumors via complexation with α-melanocyte-stimulating hormone (α-MSH) analogues conjugated with radiometals and radiohalogens, improving fluorine-18 incorporation into ligands which were otherwise unable to be synthesized and elucidating improved understandings of rhenium mechanisms and coordination sites through deuterium incorporation. This review highlights each of these rhenium-labeling cases and discusses the benefits derived therein, thus providing a useful resource for researchers intending to label unique rhenium complexes. © 2020 American Chemical Society
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    Microfluidic implementation of Ru-catalyzed methylation of amines using CO2 as carbon source
    (Akadémiai Kiadó Zrt, 2016-06-22) Perkins, G; Khatib, O; Peterson, MB; Kallinen, A; Pham, TQ; Ung, AT; Greguric, I; Pascali, G
    Carbon dioxide chemistry is an area of continuing growth in recent times, due to socioeconomic and environmental reasons. Several methods have now been reported for obtaining N-methylation on primary and secondary amines directly from CO2. We have translated in two microfluidic setups (Slug Flow [SF] and Tube-in-Tube [TiT]) a ruthenium (Ru)-catalyzed process previously reported using a pressure vessel. Here, we demonstrate how the SF approach is more efficient but requires more input to reach a steady state, while the TiT system is less efficient but more tuneable.We have tested these processes on three model amines and two radiopharmaceutical precursors that are routinely used in 11C chemistry. The microfluidic processes tested are also potentially more efficient than the pressure vessel counterpart, in terms of amount of Ru catalyst needed (1% vs. 10%) and projected reaction completion time. © 2016 Akadémiai Kiadó Zrt.
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    Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip.
    (Springer Link, 2014-10-14) Arima, V; Watts, P; Pascali, G
    Microreactors are a wide class of devices that are currently playing a prominent role in several research fields such as biology, medicine, food chemistry, environmental analysis, up to the production of compounds in organic chemistry. Several typologies of microreactors have been produced with tubular or planar shapes, of different materials and designs. In this chapter, an overview of planar microchannel-based microreactors and their application to organic chemistry is given. Initially, after recalling the main theoretical parameters of microfluidics, an introduction of the proposed technology and the main requirements to perform mixing, which is essential to perform chemical synthesis on-chip, is presented. Silicon and glass microreactors, the most common planar systems for organic chemistry, are described with the aim of pointing out the most important parameters to be taken into consideration in the planning of a specific microreactor to be used for mixing, purification or crystallization of chemicals at the microscale. Then, several applications of initially described microreactors to organic chemistry for research applications are given. In the next section, the use of planar microchannel microreactors in the field of radiochemistry is reported. The radiopharmaceutical application is not casual, being a sector in which the microreactor technology is very promising, due to the need of quickly producing small and fresh amounts of products in a controlled environment. Finally, for completeness, other approaches beyond planar microchannels are mentioned: mesoreactors towards industrial level synthesis and micro-vessels for radiochemistry. © Springer International Publishing Switzerland 2015
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    Microfluidics in radiopharmaceutical chemistry
    (Elsevier B.V., 2013-08-01) Pascali, G; Watts, P; Salvadori, PA
    The 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.
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    A novel [18F]fluoride relay reagent for radiofluorination reactions
    (John Wiley & Sons, Inc, 2019-05-26) Zhang, B; Fraser, BH; Klenner, MA; Chen, Z; Liang, SH; Massi, M; Robinson, AJ; Pascali, G
    Objectives Fluorine‐18 is the most utilized radioisotope in Positron Emission Tomography (PET), but the wide application of fluorine‐18 radiopharmaceuticals is hindered by its challenging labelling conditions. This necessitates production at centralized PET centres with highly specialized equipment including cyclotrons, hot cells, synthesizers, and HPLC capabilities, which ultimately limit the availability of fluorine‐18 tracers to those whose production has a large marketing scale (e.g., [18F]FDG). As such, many potentially important leads remain underutilized. Herein, we describe the use of [18F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres (Figure 1). Methods [18F]ESF was produced from 2,4,6‐trichlorophenylethenesulfonate using a microfluidic system and was stored on inert cartridges. The cartridges could be shipped remotely where trapped [18F]ESF was liberated by chosen solvent to a vial containing precursor and additives. The reaction mixture was then stirred and heated using a heating block. Reaction conditions including temperature, time, precursor concentration, and additives were optimised, and the radiochemical yields (RCYs) were compared with those for traditional [18F]fluoride method. Results We found that conditions of 1 mg/mL precursor, 0.5 mg/mL tetraethylammonium bicarbonate as additive, temperature of 100°C, and time of 15 min were useful to assess radiofluorination scope on commercially available precursors. The obtained RCYs were compared with those generated from traditional dried [18F]fluoride source and no statically significant difference was observed for most precursors. Some differences on RCYs, both positive and negative, were noted when novel type of precursors (i.e., boronic acids, iodonium ylides) were tested. Conclusions We have developed a method to perform radiofluorinations using a new radiofluoride relay reagent, [18F] ESF. Such method reduces the reaction equipment needed, in the simplest case to a simple heating block, single‐use vials and magnetic stir bar. Notably, this new process is not only compatible with typical commercial precursors, but also feasible to accommodate emerging precursors with novel leaving groups. © 2019 The Authors
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    Optimisation of [11C]raclopride production using a synthra GPextent system
    (Bentham Science Publishers, 2014-12-01) Perkins, G; Sheth, R; Greguric, I; Pascali, G
    The dopamine D2 receptor radiotracer [(11)C]Raclopride is used extensively in clinical and preclinical imaging. Currently, a wide range of methods to produce [(11)C]Raclopride have been developed using traditional vessel reactions as well as cartridge or captive solvent. This work reports the optimisation of the production of [(11)C]Raclopride using a Synthra GPextent, comparing various methods. With optimised conditions, we were able to obtain 4±2% (ndc) yield of [(11)C]Raclopride (100 GBq [(11)C]CO2, n = 42) in 25 min. The radiochemical purity was >95% with specific activities of 135±41 MBq/nmol at end of synthesis. © 2014 Bentham Science Publishers
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    Optimization 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, I
    Microfluidic 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
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    Purification 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, N
    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 [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.
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    Quantification of dopamine d2 receptor density and apparent affinity can be used to longitudinally assess transient striatal variations during adolescence using [11c]raclopride pet imaging
    (John Wiley & Sons, Inc., 2017-04-11) Callaghan, PD; Sobbi, PF; Safavi-Naeini, M; Wimberley, CA; Davis, E; Zahra, D; Arthur, A; Rahardjo, GL; Perkins, G; Pascali, G; Reilhac-Laborde, A; Grégoire, MC
    Background Transient increases in striatal dopamine D2 receptors occur during adolescence in rats, correlating with a developmental epoch where synaptic pruning occurs. Alteration of these processes with external stresses during adolescence may lead to affective disorders later in life. Longitudinal PET imaging with [11C]raclopride using a partial saturation design allows assessment of density (Bavail) and affinity changes (appKd) to map neurodevelopmental changes in D2 expression, which necessitates a significant level of receptors occupancy during the PET study. Aims Validate that repeated transient partial saturation of D2 receptors does not bias measures of D2 Bavail and appKd assessed using PET/CT imaging with [11C]raclopride. Methods Three cohorts of male Sprague-Dawley rats (n=6-7/group) underwent a single session of PET/CT imaging (INVEON, Siemens, USA) with [11C]raclopride (5 nmol injected i.v.) as naïve or after repeated partial saturation of D2 receptors: Cohort A received 5nmol raclopride (i.v) weekly from PND35 (postnatal day) to PND96 with PET imaging session at PND96, cohort B was scanned at PND96; Cohort C was scanned at PND35 Datasets were reconstructed (2D-FBP), coregistered with CT and time-activity data extracted using age matched atlas-based volumes of interest (striatum, cerebellum). in vivo receptor density and appKd were derived using kinetic modelling (comparisons used 1-way ANOVA follow by post hoc test). Results Expected differences in Bavail and appKd were seen between the adolescent (PND35) and the adult (PND96) cohorts, corresponding with increases in D2 receptor consistently reported in the literature using post mortem methods. No significant difference was observed in both Bavail and appKd in cohort A, exposed to repeated D2 partial saturation, compared to the naïve cohort B. Conclusion Longitudinal quantification of dopamine D2 receptor density and apparent affinity in vivo using [11C]raclopride PET imaging with partial saturation can be used to map changes in adolescent and adult rats.
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    Radiochemistry 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, R
    AbstractWe 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
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    Rhenium complexation‐dissociation strategy for fluorine‐18 labelling of bidentate PET ligands
    (John Wiley & Sons, Inc, 2019-05-26) Klenner, MA; Pascali, G; Zhang, B; Massi, M; Fraser, BH
    Objectives Pursuant to the discovery that rhenium complexation promotes fluorine‐18 radiolabelling of 1,10‐phenanthroline systems under low temperature, quasi‐aqueous conditions, which circumvent the need for azeotropic drying, we expanded our investigation towards thermal decomplexation strategies to improve the radiosynthesis of similar pyridinyl bidentate tracers. Methods Thirty‐eight compounds were synthesised based upon chloro, bromo, nitro, and fluoro substitutions of 1,10‐ phenanthroline, 2,2’‐bipyridine and 8‐hydroxyquinoline structures and their respective rhenium tricarbonyl chloride complexes. Each of these compounds, save for the nonradioactive fluoro substituted standards, were reacted (>n = 8) under microfluidic conditions with tetraethyl ammonium [18F]fluoride in anhydrous DMSO solvent with increasing reaction temperatures ranging from 50°C to 190°C in 20°C increments. All other parameters such as the precursor quantity, radioactivity, and flow rate/reaction time were kept constant (0.08 μmol, 29 ± 10 MBq, 20 μL·min−1/47 s, respectively). Radiochemical yields (RCYs) for each reaction were then calculated from the Radio‐HPLC peak integrations of the non‐isolated products. Results High RCYs were observed for the [18F]fluoride substitution of rhenium complexed 1,10‐phenanthroline structures (up to 91%) at temperatures ≤90°C, which could prove useful as a novel method for producing PET‐optical tracers given the optical emission properties of rhenium. Good RCYs were also observed for the 2,2’‐bipyridine rhenium complexes, peaking at 84% at 130°C in one example, which then dissociated to form the radiolabelled ligand in 82% RCY at a higher temperature of 190°C, as shown in Figure 1. Radiolabelling of these ligands was unsuccessful under conventional conditions using dry [18F]fluoride, thus establishing rhenium complexation‐dissociation as a novel method for radiolabelling. The fluorine‐18 labelling of 8‐ hydroxyquinoline structures was also tested as a means of improving the radiosynthesis of Alzheimer's disease imaging PET tracers such as [18F]CABS13. While preliminary rhenium complexation‐dissociation experiments have not yet improved on the radiosynthesis of [18F]CABS13 (5% RCY of ligand & 18% RCY of rhenium complex vs 19±5% RCY of ligand in literature), such experiments have enabled the radiosynthesis of related structures, which could not be radiolabelled under conventional conditions using dry [18F]fluoride (eg, [18F]5‐ fluoro‐8‐hydroxyquinoline). Conclusions We report a novel radiofluorination method utilising the rhenium complexation of pyridinyl bidentate structures. This method facilitates radiolabelling of certain analogues of 2,2’‐bipyridine and 8‐hydroxyquinoline structures, which do not radiolabel under conventional conditions. Investigations into monopyridine structures and the development of milder methods of decomplexation are currently ongoing. © 2019 The Authors