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Design and implementation of an automated DT-PhotoFluor radiosynthesis module for 18F-fluorination of aliphatic, branched chain amino acids

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Abstract

Herein we report the automation and scale-up of a photofluorination process key to the production of branched-chain aliphatic radiotracers such as (S)-5-[18F]fluorohomoleucine ((S)-5-[18F]]FHL). (S)-5-[18F]FHL is a leucine analogue that is primarily taken up by the L-type amino acid transporter (LAT or System L). LAT1 expression levels correlate closely with tumor proliferation, angiogenesis, and treatment outcomes, making it an attractive target for molecular imaging of cancer. We have previously synthesized (S)-5-[18F]FHL and tested this tracer in mice bearing PC3 (prostate) or U87 (glioma) xenografts in order to establish its feasibility for detecting and monitoring treatment for a broad range of cancers. In this study, the radiosynthesis of 5-[18F]FHL is demonstrated on an automated DT-PhotoFluor module with a radiochemical yield of 20.1 ± 4.8% (n = 3), radiochemical purity of 94.5 ± 4.9% (n = 3), and a synthesis time of ~ 75 min. The reported DT-PhotoFluor module will allow for higher molar activity, better reproducibility, and reduced radiation exposure for upcoming first-in-human studies.

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Data Availability

Data sets reported here are available upon requested from the corresponding author.

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Acknowledgements

This study is supported by Canadian Institute for Cancer Research – Innovation to Impact grant (#705808). TRIUMF receives federal funding via a contribution agreement with the National Research Council of Canada. Z.Y. gratefully acknowledges financial support from China Scholarship Council (#202107260030). We would like to thank TRIUMF's TR13 operation group consisting of Spencer Staiger, Toni Epp, Ryley Morgan, and led by David Prevost.

Funding

This work was supported by Canadian Cancer Society Research Institute, 705808, Paul Schaffer, China Scholarship Council, 202107260030, Zheliang Yuan.

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Author notes

  1. Gokce Engudar and Zheliang Yuan contributed equally to this work.

Authors and Affiliations

  1. Life Sciences Division, TRIUMF, Vancouver, British Columbia, V6T 2A3, Canada

    Gokce Engudar, Hua Yang, Chelsey Currie, Stuart McDiarmid & Paul Schaffer

  2. Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S2, Canada

    Zheliang Yuan, Matthew B. Nodwell, Hua Yang, Robert Britton & Paul Schaffer

  3. Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, College of Chemistry and Materials Sciences, Zhejiang Normal University, Jinhua, 321004, Zhejiang, China

    Zheliang Yuan

  4. Department of Radiology, University of British Columbia, Vancouver, British Columbia, V5Z 1M9, Canada

    Paul Schaffer

Authors
  1. Gokce Engudar
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  2. Zheliang Yuan
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  3. Matthew B. Nodwell
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  4. Hua Yang
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  7. Robert Britton
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  8. Paul Schaffer
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Corresponding authors

Correspondence to Robert Britton or Paul Schaffer.

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Highlights

• Decatungstate-mediated, photocatalytic radiofluorination is a new approach for producing libraries of fluorine-18 (F-18) labelled branch-chain, aliphatic amino acids with potential use in positron emission tomography (PET).

• An automated decatungstate photofluorination (DT-PhotoFluor) module has been designed and developed that improves process reproducibility while minimizing radiation exposure to radiochemistry personnel.

• Initial testing of the DT-PhotoFluor module for the radiofluorination of (S)-5-[18F]fluorohomoleucine showed comparable labeling results (e.g., radiochemical yield and radiochemical purity) to the manual radiosynthesis process.

• This study demonstrates the robustness and potential application of an automated flow module for radiosynthesis of 18F-labeled aliphatic, branched-chain amino acids for eventual preclinical and clinical trials.

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Engudar, G., Yuan, Z., Nodwell, M.B. et al. Design and implementation of an automated DT-PhotoFluor radiosynthesis module for 18F-fluorination of aliphatic, branched chain amino acids. J Flow Chem 14, 11–21 (2024). https://doi.org/10.1007/s41981-024-00314-3

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