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This article describes a sequential Ir/Cu-mediated process for the meta- selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp 2 )-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [ 18 F]tetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochemical yield and radiochemical purity. This entire process is performed on a benchtop without Schlenk or glovebox techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FX FN module with 1,3-dimethoxybenzene and a meta- tyrosine derivative. The products, [ 18 F]1-fluoro-3,5-dimethoxybenzene and an 18 F-labeled meta- tyrosine derivative, were obtained in 37 ± 5% isolated radiochemical yield and >99% radiochemical purity and 25% isolated radiochemical yield and 99% radiochemical purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity ( A m ), respectively.

[ 18 F]6-fluoro-L-DOPA ([ 18 F]FDOPA) is a diagnostic radiopharmaceutical for positron emission tomography (PET) imaging that is used to image Parkinson's disease, brain tumors, and focal hyperinsulinism of infancy. Despite these important applications, [ 18 F]FDOPA PET remains underutilized because of synthetic challenges associated with accessing the radiotracer for clinical use; these stem from the need to radiofluorinate a highly electron-rich catechol ring in the presence of an amino acid. To address this longstanding challenge in the PET radiochemistry community, we have developed a one-pot, two-step synthesis of high-molar-activity [ 18 F]FDOPA by Cu-mediated fluorination of a pinacol boronate (BPin) precursor. The method is fully automated, has been validated to work well at two separate sites (an academic facility with a cyclotron on site and an industry lab purchasing [ 18 F]fluoride from an outside vendor), and provides [ 18 F]FDOPA in reasonable radiochemical yield (2.44 ± 0.70 GBq, 66 ± 19 mCi, 5 ± 1%), excellent radiochemical purity (>98%) and high molar activity (76 ± 30 TBq/mmol, 2,050 ± 804 Ci/mmol), n = 26. Herein we report a detailed protocol for the synthesis of [ 18 F]FDOPA that has been successfully implemented at two sites and validated for production of the radiotracer for human use.

A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-[ 11 C]-nitriles is reported. This method is operationally simple, uses commercially available reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity [ 11 C]perampanel in 10% nondecay-corrected radiochemical yield (RCY).

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K(18)F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [(18)F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors.

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K18F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [18F]FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors. [ABSTRACT FROM AUTHOR]

[Display omitted] • Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in cancer and brain health illnesses. • No suitable fluorine-18 labeled GSK-3 radiotracer for positron emission tomography (PET) exists. • Two oxazole-4-carboxamides were labeled with [18F]fluoride. • Radiotracers were evaluated in rodents and in non-human primate showing good brain uptake. • [18F]OCM-49 and [18F]OCM-50 are promising tracers for imaging of GSK-3 in the brain. Glycogen synthase kinase 3 (GSK-3) is an enzyme that is dysregulated in oncology, neurodegeneration, neuroinflammation and several mental health illnesses. As such, GSK-3 is a long-sought after target for positron emission tomography (PET) imaging and therapeutic intervention. Herein, we report on the development and radiofluorination of two oxazole-4-carboxamides, including one bearing a non-activated aromatic ring. Both compounds demonstrated excellent selectivity in a kinase screen and inhibit GSK-3 with high affinity. [18F]OCM-49 was synthesized from [18F]fluoride using a copper-mediated reaction of an aryl boronic acid precursor, while [18F]OCM-50 used a trimethylammonium triflate precursor, and both radiotracers were translated for preclinical PET imaging in rodents. Due to superior radiochemical yields and brain uptake (peak standardized uptake value of ∼2.0), [18F]OCM-50 was further evaluated in non-human primate and also showed good brain uptake and rapid clearance. Further studies to consider clinical translation of both radiotracers are underway. [ABSTRACT FROM AUTHOR]