Proof-of-concept optimization of a copper-mediated <sup>18</sup>F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Lu, Yingqing; He, Yingfang; Schibli, Roger; Mu, Linjing; van Dam, R. Michael

doi:10.1039/d3lc00735a

Cited by 4 publications

(3 citation statements)

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“…This could potentially be attributed to the fast degradation of Cu(OTf) 2 due to exposure to atmosphere in the open droplet reaction format, or low effectiveness of Cu(OTf) 2 to promote the fluorination in a droplet reaction. In our previous report, 20 the preparation of [ 18 F]YH149 via a similar Cu-mediated route but using the copper reagent Cu(Py) 4 (OTf) 2 resulted in a RCC of 0% ( n = 2) in the absence of pyridine. Interestingly, in the current study, the synthesis of [ 18 F]FBnTP using the copper reagent Cu(OTf) 2 even with the addition of pyridine led to a similar outcome (no conversion).…”

Section: Resultsmentioning

confidence: 99%

“…19) and a novel monoacylglycerol lipase (MAGL) ligand, [ 18 F]YH-149. 20 Droplet radiochemistry offers advantages of minimal reagent cost, rapid synthesis time, high yield, high molar activity, and low space and infrastructure requirements. A further advantage of droplet radiochemistry is the ability to perform high-throughput optimization via arrays of droplet reactions performed in parallel.…”

Section: Introductionmentioning

confidence: 99%

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Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach

Lu,

Collins,

Lin

et al. 2024

Lab Chip

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach

Lu,

Collins,

Lin

et al. 2024

Lab Chip

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“…Several recent reports have made strides in addressing the engineering and analytical challenges required for HTE radiofluorination. For instance, microfluidic flow platforms have been employed to run sequential radiolabeling reactions. − In a significant development, van Dam and coworkers leveraged advanced droplet microreactors for radiochemistry in combination with rapid quantification of rTLC plates using Cherenkov radiation. − This serves as a platform for high-throughput radiochemical exploration using microfluidic arrays . These studies demonstrate the potential impact of parallel reaction screening and analysis on radiochemical reaction optimization.…”

Section: Introductionmentioning

confidence: 99%

Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration

Webb,

Cheng,

Winton

et al. 2024

J. Am. Chem. Soc.

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Positron emission tomography is a widely used imaging platform for studying physiological processes. Despite the proliferation of modern synthetic methodologies for radiolabeling, the optimization of these reactions still primarily relies on inefficient one-factor-at-a-time approaches. High-throughput experimentation (HTE) has proven to be a powerful approach for optimizing reactions in many areas of chemical synthesis. However, to date, HTE has rarely been applied to radiochemistry. This is largely because of the short lifetime of common radioisotopes, which presents major challenges for efficient parallel reaction setup and analysis using standard equipment and workflows. Herein, we demonstrate an effective HTE workflow and apply it to the optimization of copper-mediated radiofluorination of pharmaceutically relevant boronate ester substrates. The workflow utilizes commercial equipment and allows for rapid analysis of reactions for optimizing reactions, exploring chemical space using pharmaceutically relevant aryl boronates for radiofluorinations, and constructing large radiochemistry data sets.

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Transition-Metal-Mediated Radiohalogenation using Aryl Boron Reagents

Sutherland,

Burianova,

McErlain

2024

Synthesis

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Biomolecules labeled with radioisotopes of iodine and fluorine play a major role in science and medicine, with a range of applications including molecular imaging of disease, as radiopharmaceuticals for therapy and as tools for drug discovery. Due to the relative stability of Csp2–halogen bonds, radioiodine and radiofluorine labels are commonly incorporated into tracers via arene substitution. The wide availability of aryl boron reagents has led to their use for the development of radioiodination and radiofluorination methods, particularly using transition-metal complexes for accelerated reactions. Here, we review the range of transition-metal-mediated methods that have been developed for radiohalogenation of aryl boron compounds. Applications of these transformations for the preparation of molecular imaging agents and the use of new technologies to advance automated synthesis or high-throughput discovery are also described.1 Introduction2 Radioiodination Using Aryl Boron Reagents2.1 Applications of Copper-Mediated Radioiodination Reactions3 Radiofluorination Using Aryl Boron Reagents3.1 Radiofluorination Using Palladium, Nickel and Silver Complexes3.2 Radiofluorination Using Copper Complexes3.3 Applications of Copper-Mediated Radiofluorination Reactions3.4 New Technology for Copper-Mediated Radiofluorination Reactions4 Conclusions

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Proof-of-concept optimization of a copper-mediated ¹⁸F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Abstract: Arrays of parallel droplet reactions enable high-speed optimization, and discovered conditions can be immediately scaled for use on conventional instruments.

Cited by 4 publications

References 53 publications

Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach

Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach

Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration

Transition-Metal-Mediated Radiohalogenation using Aryl Boron Reagents

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Proof-of-concept optimization of a copper-mediated 18F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Abstract: Arrays of parallel droplet reactions enable high-speed optimization, and discovered conditions can be immediately scaled for use on conventional instruments.

Cited by 4 publications

References 53 publications

Scalable droplet-based radiosynthesis of [18F]fluorobenzyltriphenylphosphonium cation ([18F]FBnTP) via a “numbering up” approach

Scalable droplet-based radiosynthesis of [18F]fluorobenzyltriphenylphosphonium cation ([18F]FBnTP) via a “numbering up” approach

Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration

Transition-Metal-Mediated Radiohalogenation using Aryl Boron Reagents

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Proof-of-concept optimization of a copper-mediated ¹⁸F-radiosynthesis of a novel MAGL PET tracer on a high-throughput microdroplet platform and its macroscale translation

Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach

Scalable droplet-based radiosynthesis of [¹⁸F]fluorobenzyltriphenylphosphonium cation ([¹⁸F]FBnTP) via a “numbering up” approach