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

Gokce Engudar; Zheliang Yuan; Matthew B. Nodwell; Hua Yang; Chelsey Currie; Stuart McDiarmid; Robert Britton; Paul Schaffer

doi:10.1007/s41981-024-00314-3

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

Gokce Engudar
, Zheliang Yuan
, Matthew B. Nodwell
, Hua Yang
, Chelsey Currie
, Stuart McDiarmid
, Robert Britton
, Paul Schaffer

Isotope Applications Research

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English
Pages (from-to)	11-21
Number of pages	11
Journal	Journal of Flow Chemistry
Volume	14
Issue number	1
DOIs	https://doi.org/10.1007/s41981-024-00314-3
State	Published - Mar 2024

Funding

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

Keywords

(S)-5-[F]fluorohomoleucine
Automated radiosynthesis
LAT transport
Photocatalytic F-fluorination

Access to Document

10.1007/s41981-024-00314-3

Cite this

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

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 \textasciitilde{} 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.",

keywords = "(S)-5-[F]fluorohomoleucine, Automated radiosynthesis, LAT transport, Photocatalytic F-fluorination",

author = "Gokce Engudar and Zheliang Yuan and Nodwell, \{Matthew B.\} and Hua Yang and Chelsey Currie and Stuart McDiarmid and Robert Britton and Paul Schaffer",

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AU - Engudar, Gokce

AU - Yuan, Zheliang

AU - Nodwell, Matthew B.

AU - Yang, Hua

AU - Currie, Chelsey

AU - McDiarmid, Stuart

AU - Britton, Robert

AU - Schaffer, Paul

N1 - Publisher Copyright: © Akadémiai Kiadó 2024.

PY - 2024/3

Y1 - 2024/3

N2 - 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.

AB - 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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KW - LAT transport

KW - Photocatalytic F-fluorination

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