<sup>18</sup>F-Branched-Chain Amino Acids: Structure–Activity Relationships and PET Imaging Potential

Nodwell, Matthew B.; Yang, Hua; Malik, Noeen; Čolović, Milena; Wagner, Bjoern; Martin, Rainer E.; Bénard, François; Schaffer, Paul; Britton, Robert

doi:10.2967/jnumed.118.220483

Cited by 13 publications

(12 citation statements)

References 34 publications

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“…Recently, a report from Merck highlighted the utility of this catalyst for oxidation of C–H bonds in aliphatic amines, MacMillan reported the coupling of DT catalysis with nickel-mediated cross-coupling reactions to form C–C bonds, and Melchiorre demonstrated asymmetric conjugate addition of DT-generated carbon radicals . In work from our laboratories, we paired DT-catalyzed HAT with fluorine atom transfer from N -fluorobenzenesulfonimide (NFSI) to affect the direct fluorination of aliphatic , and benzylic C–H bonds . Further, we recently disclosed the direct 18 F-fluorination of amino acids , and peptides in aqueous media using DT as a means to generate positron emission tomography (PET) imaging agents for oncology.…”

Section: Introductionmentioning

confidence: 99%

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

et al. 2019

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The site-selective fluorination of unactivated C(sp3)-H bonds provides unique opportunities to rapidly alter drug properties or generate radiotracers for positron emission tomography (PET) imaging. Toward this goal, photoactivated decatungstate (DT) is capable of generating carbon radicals through hydrogen atom transfer that subsequently undergo fluorination by reaction with N-fluorobenzenesulfonimide (NFSI) or [18F]NFSI. This process enables C(sp3)-H fluorination of a wide range of aliphatic compounds, though reaction rates can be highly variable and limit applications in radiotracer synthesis. Here, we demonstrate that cationic ammonium functions in aliphatic molecules promote formation of a precursor complex with DT that significantly increases the rate of C–H abstraction. The general utility of this rate-accelerating electrostatic effect is demonstrated on more than 30 ammonium-containing molecules, including amino acids, heterocycles, and pseudopeptides. Moreover, this effect is highlighted in the rapid production of [18F]Glu-U-FHLeu, a 18F-labeled prostate specific membrane antigen (PSMA)-binding ligand.

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Section: Introductionmentioning

confidence: 99%

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

et al. 2019

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“…Subsequent studies on the fluorination of leucine-containing polypeptides with NFSI showed a general solution for enhancement of labeling efficiency through an ammonium group-mediated catalyst−substrate complexation (Scheme 101). 288,289 The NFSI and NaDT mediated fluorination of peptidic structures was also applied in a SAR study of [ 18 F]-labeled leucine analogues as novel potential PET tracers. 289 In vitro uptake studies in a prostate-specific membrane antigen (PMSA)-negative PC3 showed good correlation with both Ltype amino acid transporters affinity studies and subsequent in vivo biodistribution and dynamic PET imaging studies in mice bearing U-87 cell line xenografs.…”

Section: Isotope Labelingmentioning

confidence: 99%

“…288,289 The NFSI and NaDT mediated fluorination of peptidic structures was also applied in a SAR study of [ 18 F]-labeled leucine analogues as novel potential PET tracers. 289 In vitro uptake studies in a prostate-specific membrane antigen (PMSA)-negative PC3 showed good correlation with both Ltype amino acid transporters affinity studies and subsequent in vivo biodistribution and dynamic PET imaging studies in mice bearing U-87 cell line xenografs.…”

Section: Isotope Labelingmentioning

confidence: 99%

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Photocatalysis in the Life Science Industry

et al. 2021

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In the pursuit of new pharmaceuticals and agrochemicals, chemists in the life science industry require access to mild and robust synthetic methodologies to systematically modify chemical structures, explore novel chemical space, and enable efficient synthesis. In this context, photocatalysis has emerged as a powerful technology for the synthesis of complex and often highly functionalized molecules. This Review aims to summarize the published contributions to the field from the life science industry, including research from industrial-academic partnerships. An overview of the synthetic methodologies developed and strategic applications in chemical synthesis, including peptide functionalization, isotope labeling, and both DNA-encoded and traditional library synthesis, is provided, along with a summary of the state-of-the-art in photoreactor technology and the effective upscaling of photocatalytic reactions.

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“…This approach creates a framework for the development of AA radiopharmaceuticals that are analogous to their canonical counterparts ( Figure 3). Furthermore, Britton and coworkers developed a method for the electrophilic radiofluorination of unactivated C-H bonds in hydrophobic amino acids ( Figure 3) to produce 18 F-labeled AAs that can visualize glioblastoma and prostate adenocarcinoma xenografts [121,122]. 18 F-labeled AAs by replacing the carboxylate group (-COO − ) with an isosteric trifluoroborate (BF3 − ) group that can be radiolabeled through an isotope exchange reaction [120].…”

Section: Probes Based On Bioactive Moleculesmentioning

confidence: 99%

Insight into the Development of PET Radiopharmaceuticals for Oncology

Lau

Rousseau

Kwon³

et al. 2020

Cancers

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While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both with respect to their preclinical and clinical evaluation. We also provide a guideline for the proper selection of a radionuclide and the appropriate labeling strategy to access a tracer with optimal imaging qualities. Finally, we summarize the methodology of their evaluation in in vitro and animal models and the road to clinical translation. This review is intended to be a primer for newcomers to the field and give insight into the workflow of developing radiopharmaceuticals.

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¹⁸F-Branched-Chain Amino Acids: Structure–Activity Relationships and PET Imaging Potential

Cited by 13 publications

References 34 publications

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

Photocatalysis in the Life Science Industry

Insight into the Development of PET Radiopharmaceuticals for Oncology

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18F-Branched-Chain Amino Acids: Structure–Activity Relationships and PET Imaging Potential

Cited by 13 publications

References 34 publications

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [18F]- and [19F]NFSI in Small Molecules and Peptide Mimics

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [18F]- and [19F]NFSI in Small Molecules and Peptide Mimics

Photocatalysis in the Life Science Industry

Insight into the Development of PET Radiopharmaceuticals for Oncology

Contact Info

Product

Resources

About

¹⁸F-Branched-Chain Amino Acids: Structure–Activity Relationships and PET Imaging Potential

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics

Electrostatic Effects Accelerate Decatungstate-Catalyzed C–H Fluorination Using [¹⁸F]- and [¹⁹F]NFSI in Small Molecules and Peptide Mimics