In-loop flow [11C]CO2 fixation and radiosynthesis of N,N′-[11C]dibenzylurea

Joseph Downey; Salvatore Bongarzone; Stefan Hader; Antony D. Gee

doi:10.1002/jlcr.3568

In-loop flow [¹¹C]CO₂ fixation and radiosynthesis of N,N′-[¹¹C]dibenzylurea

Joseph Downey, Salvatore Bongarzone, Stefan Hader, Antony D. Gee^*

^*Corresponding author for this work

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

13 Citations (Scopus)

Abstract

Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([¹¹C]CO₂), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [¹¹C]CO₂ fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [¹¹C]CO₂, and the advantages afforded by the use of a loop-based system used in ¹¹C-methylation and ¹¹C-carboxylation reactions inspired us to apply the [¹¹C]CO₂ fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [¹¹C]CO₂ fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [¹¹C]CO₂ using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N′-[¹¹C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [¹¹C]CO₂ fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [¹¹C]CO₂ trapping/fixation reactions for the production of PET radiotracers.

Original language	English
Journal	JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
Early online date	22 Dec 2017
DOIs	https://doi.org/10.1002/jlcr.3568
Publication status	E-pub ahead of print - 22 Dec 2017

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10.1002/jlcr.3568Licence: CC BY

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title = "In-loop flow [11C]CO2 fixation and radiosynthesis of N,N′-[11C]dibenzylurea",

abstract = "Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop-based system used in 11C-methylation and 11C-carboxylation reactions inspired us to apply the [11C]CO2 fixation {"}in-loop.{"} In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [11C]CO2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N′-[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.",

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T1 - In-loop flow [11C]CO2 fixation and radiosynthesis of N,N′-[11C]dibenzylurea

AU - Downey, Joseph

AU - Bongarzone, Salvatore

AU - Hader, Stefan

AU - Gee, Antony D.

PY - 2017/12/22

Y1 - 2017/12/22

N2 - Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop-based system used in 11C-methylation and 11C-carboxylation reactions inspired us to apply the [11C]CO2 fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [11C]CO2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N′-[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.

AB - Cyclotron-produced carbon-11 is a highly valuable radionuclide for the production of positron emission tomography (PET) radiotracers. It is typically produced as relatively unreactive carbon-11 carbon dioxide ([11C]CO2), which is most commonly converted into a more reactive precursor for synthesis of PET radiotracers. The development of [11C]CO2 fixation methods has more recently enabled the direct radiolabelling of a diverse array of structures directly from [11C]CO2, and the advantages afforded by the use of a loop-based system used in 11C-methylation and 11C-carboxylation reactions inspired us to apply the [11C]CO2 fixation "in-loop." In this work, we developed and investigated a new ethylene tetrafluoroethylene (ETFE) loop-based [11C]CO2 fixation method, enabling the fast and efficient, direct-from-cyclotron, in-loop trapping of [11C]CO2 using mixed DBU/amine solutions. An optimised protocol was integrated into a proof-of-concept in-loop flow radiosynthesis of N,N′-[11C]dibenzylurea. This reaction exhibited an average 78% trapping efficiency and a crude radiochemical purity of 83% (determined by radio-HPLC), giving an overall nonisolated radiochemical yield of 72% (decay-corrected) within just 3 minutes from end of bombardment. This proof-of-concept reaction has demonstrated that efficient [11C]CO2 fixation can be achieved in a low-volume (150 μL) ETFE loop and that this can be easily integrated into a rapid in-loop flow radiosynthesis of carbon-11-labelled products. This new in-loop methodology will allow fast radiolabelling reactions to be performed using cheap/disposable ETFE tubing setup (ideal for good manufacturing practice production) thereby contributing to the widespread usage of [11C]CO2 trapping/fixation reactions for the production of PET radiotracers.

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DO - 10.1002/jlcr.3568

M3 - Article

AN - SCOPUS:85038835892

SN - 0362-4803

JO - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

JF - JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS

ER -

In-loop flow [¹¹C]CO₂ fixation and radiosynthesis of N,N′-[¹¹C]dibenzylurea

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