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A simple technique for the preparation of [18F]HF has been developed and applied to the generation of an [18F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[18F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorohydrin PET imaging agents in good yields and high molar activities. [ABSTRACT FROM AUTHOR]

This report describes a Pd-mediated C–H radiofluorination of 8-methylquinoline derivatives with no-carrier-added Ag[18F]F. To achieve this transformation, a new method was developed for the generation of Ag[18F]F using a sep-pak cartridge. The C–H radiofluorination was then optimized and applied to a series of substituted 8-methylquinoline derivatives. Finally, this method was fully automated using a radiochemistry synthesis module. [ABSTRACT FROM AUTHOR]

Green strategies for late-stage fluorination with 18F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process (azeotropic drying, nucleophilic fluorination, purification and formulation), have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging. [ABSTRACT FROM AUTHOR]

The most prominent myocardial voltage-gated sodium channel, Na V 1.5, is a major drug target for treating cardiovascular disease. However, treatment determination and therapeutic development are complicated partly by an inadequate understanding of how the density of SCN5A, the gene that encodes Na V 1.5, relates to treatment response and disease prognosis. To address these challenges, imaging agents derived from Na V 1.5 blocking therapeutics have been employed in positron emission tomography (PET) imaging to infer how SCN5A expression relates to human disease in vivo . Herein, we describe the preparation of a novel fluorine-18 labelled analogue of lidocaine, a known Na V 1.5 inhibitor, and compare this agent to a previously described analogue. Evidence from rodent and non-human primate PET imaging experiments suggests that the imaging utility of these agents may be limited by rapid metabolism and clearance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the research reported in this paper., (This journal is © The Royal Society of Chemistry.)

A one-pot two-step synthesis of 6-[ 18 F]fluoro-l-DOPA ([ 18 F]FDOPA) has been developed involving Cu-mediated radiofluorination of a pinacol boronate ester precursor. The method is fully automated, provides [ 18 F]FDOPA in good activity yield (104 ± 16 mCi, 6 ± 1%), excellent radiochemical purity (>99%) and high molar activity (3799 ± 2087 Ci mmol -1 ), n = 3, and has been validated to produce the radiotracer for human use.

A simple technique for the preparation of [18F]HF has been developed and applied to the generation of an [18F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[18F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorohydrin PET imaging agents in good yields and high molar activities.

This report describes a Pd-mediated C-H radiofluorination of 8-methylquinoline derivatives with no-carrier-added Ag[18F]F. To achieve this transformation, a new method was developed for the generation of Ag[18F]F using a sep-pak cartridge. The C-H radiofluorination was then optimized and applied to a series of substituted 8-methylquinoline derivatives. Finally, this method was fully automated using a radiochemistry synthesis module.

There is considerable interest in using positron emission tomography (PET) imaging to understand the function of dopamine D 3 receptors. Due to high sequence homology with D 2 receptors, development of D 3 -selective PET radiotracers has been challenging. In an effort to overcome this issue, we report the radiosynthesis of a new selective D 3 ligand with carbon-11 ( [ 11 C] 1 ), and its initial preclincial evaluation as a potential PET radiotracer for in vivo imaging of D 3 receptors. [ 11 C] 1 was prepared via [ 11 C]CO 2 fixation in 0.1% non-corrected radiochemical yield, good radiochemical purity (>95%) and high specific activity (>2000 Ci mmol -1 ). [ 11 C] 1 exhibited specific binding to D 3 receptors using ex vivo autoradiography experiments with rat brain, but only 14-fold selectivity over D 2 receptors which is lower than the 1400-fold value reported previously for cell studies. Rodent PET imaging revealed reasonable uptake of the radiotracer in areas of the brain known to be rich in D 3 receptors.

Radiolabeled erythrocytes have multiple applications in nuclear medicine, including blood pool imaging. Historically they have been labeled with SPECT radionuclides. A PET blood pool imaging agent is highly desirable as it would improve clinical applications with better image quality and resolution, higher sensitivity, and dynamic scanning capabilities. With the coming of age of modern 68 Ge/ 68 Ga generator systems, gallium-68 is now widely accessible. In this paper we describe an updated method for the preparation of 68 Ga-labeled erythrocytes and their preliminary use in rodent blood pool imaging. A novel automated synthesis of [ 68 Ga]oxine using a 68 Ga/ 68 Ge generator and automated synthesis module is reported. [ 68 Ga]Oxine was synthesized in 50 ± 5% ( n = 3) non-decay corrected radiochemical yield and >99% radiochemical purity. Rat and human erythrocytes were successfully labeled with the complex in 42% RCY, and the 68 Ga-labeled erythrocytes have been shown to clearly image the blood pool in a healthy rat. Human erythrocytes labelled with [ 68 Ga]oxine were shown to be viable up to 2 hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post-labelling. Further optimization of the labeling method to translate for use in human cardiac and oncologic blood pool PET imaging studies, is underway.

Green strategies for late-stage fluorination with (18)F, in which ethanol and water are the only solvents used throughout the entire radiolabeling process (azeotropic drying, nucleophilic fluorination, purification and formulation), have been developed and applied to the radiosyntheses of a range of radiopharmaceuticals commonly employed in clinical PET imaging.

The phenol of 1-(3-(1H-imidazol-1-yl)propyl)-3-(4-hydroxy-3-methoxyphenyl)thiourea was selectively carbon-11 labelled to generate [ 11 C]PBD150 in 7.3% yield from [ 11 C]methyl triflate (non-decay corrected; radiochemical purity ≥95%, specific activity = 5.7 Ci/µmol, n=5). Evaluation of [ 11 C]PBD150 by small animal PET imaging (mouse and rat) determined it does not permeate the blood brain barrier, indicating previously described therapeutic effect in transgenic mice was likely not the result of inhibiting central nervous system glutaminyl cyclase.

The last 2-3 years have seen numerous relationships develop between organometallic chemists, fluorine chemists and PET Centers around the world. These collaborations have led to the development of many new strategies for the late-stage introduction of fluorine-18 into complex bioactive molecules. In this perspective we highlight recent developments and key milestones since 2011.