Automating the production of [Fe18FF2(BnMe2-tacn)] and investigating radiostabilisers for use with high-activity [18F]F−
Automating the production of [Fe18FF2(BnMe2-tacn)] and investigating radiostabilisers for use with high-activity [18F]F−
The manual radiofluorination and purification of [FeF3(BnMe2-tacn)] (tacn = 1,4,7-triazacyclononane) using 18F− in aqueous EtOH has been translated to a GE FASTLab™ automatic synthesis platform and optimised by conducting a series of low-activity radiolabelling experiments to explore the effects of varying the precursor concentration, temperature, heating time, addition of NaOAc buffer and EtOH:H2O ratio. The optimal conditions were determined to be 1 mg/mL of the precursor being heated at 120 °C for 10 min in 75 %:25 % EtOH:H2O containing 18F−, with elution using 10 mM NaOAc, giving 61 % radiochemical yield (RCY). These conditions were then employed with high-activity 18F− giving a 97 % radiochemical purity (RCP) at t = 0, which decreases by 22 % over 5 h. Sodium ascorbate, nicotinamide and p-benzoic acid (pABA) were then tested as potential radiostabilisers for this system, initially using low-activity 18F−. These experiments revealed very rapid defluorination of the radioproduct in the presence of sodium ascorbate. In contrast, both nicotinamide and pABA appear to be effective radiostabilisers, resulting in RCP values of 91 % and 89 %, respectively, after 2 h, which compare with an RCP of 81 % under analogous conditions at t = 2 h in their absence. High-activity experiments were then undertaken with addition of 5 mg/mL of nicotinamide, with a radio-active concentration (RAC) of 220 MBq/mL, giving RCY of 26 % and following purification, RCP values for the [Fe18FF2(BnMe2-tacn)] product of 97 % at t = 0 and 86 % after 3 h.
IUPAC Distinguished Women in Chemistry and Chemical Engineering, Women in Science, benzyl dimethyl tacn, high activity 18F, iron complex, isotopic exchange, radiofluorine, radiostabilisers, high activity F, 2023 IUPAC Distinguished Women in Chemistry and Chemical Engineering
57-68
Woodward, Madeleine S.
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Runacres, Danielle E.
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Grigg, Julian
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Khan, Imtiaz
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Levason, William
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McRobbie, Graeme
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Reid, Gillian
37d35b11-40ce-48c5-a68e-f6ce04cd4037
5 January 2024
Woodward, Madeleine S.
904ae45d-221e-4ce3-ab2a-325451139bec
Runacres, Danielle E.
aae55f94-b99a-4e9f-9d1b-8bcd3f2a93b6
Grigg, Julian
fb292b6d-105f-468c-b056-d8fae1dc79b5
Khan, Imtiaz
e11ffb13-7192-47ba-a19c-5e360fb7f50f
Levason, William
e7f6d7c7-643c-49f5-8b57-0ebbe1bb52cd
McRobbie, Graeme
b12f273f-dd78-4ff8-a423-b0b5158091c7
Reid, Gillian
37d35b11-40ce-48c5-a68e-f6ce04cd4037
Woodward, Madeleine S., Runacres, Danielle E., Grigg, Julian, Khan, Imtiaz, Levason, William, McRobbie, Graeme and Reid, Gillian
(2024)
Automating the production of [Fe18FF2(BnMe2-tacn)] and investigating radiostabilisers for use with high-activity [18F]F−.
Pure and Applied Chemistry, 96 (1), .
(doi:10.1515/pac-2023-1008).
Abstract
The manual radiofluorination and purification of [FeF3(BnMe2-tacn)] (tacn = 1,4,7-triazacyclononane) using 18F− in aqueous EtOH has been translated to a GE FASTLab™ automatic synthesis platform and optimised by conducting a series of low-activity radiolabelling experiments to explore the effects of varying the precursor concentration, temperature, heating time, addition of NaOAc buffer and EtOH:H2O ratio. The optimal conditions were determined to be 1 mg/mL of the precursor being heated at 120 °C for 10 min in 75 %:25 % EtOH:H2O containing 18F−, with elution using 10 mM NaOAc, giving 61 % radiochemical yield (RCY). These conditions were then employed with high-activity 18F− giving a 97 % radiochemical purity (RCP) at t = 0, which decreases by 22 % over 5 h. Sodium ascorbate, nicotinamide and p-benzoic acid (pABA) were then tested as potential radiostabilisers for this system, initially using low-activity 18F−. These experiments revealed very rapid defluorination of the radioproduct in the presence of sodium ascorbate. In contrast, both nicotinamide and pABA appear to be effective radiostabilisers, resulting in RCP values of 91 % and 89 %, respectively, after 2 h, which compare with an RCP of 81 % under analogous conditions at t = 2 h in their absence. High-activity experiments were then undertaken with addition of 5 mg/mL of nicotinamide, with a radio-active concentration (RAC) of 220 MBq/mL, giving RCY of 26 % and following purification, RCP values for the [Fe18FF2(BnMe2-tacn)] product of 97 % at t = 0 and 86 % after 3 h.
Text
radiochem paper - PAChem final accepted version
- Accepted Manuscript
More information
Accepted/In Press date: 14 December 2023
e-pub ahead of print date: 5 January 2024
Published date: 5 January 2024
Additional Information:
This research was funded by a CASE studentship to M.S.W from GE Healthcare and EPSRC grant number EP/R513325/1, and through the EPSRC Mithras Programme Grant (EP/S032789/1)
Publisher Copyright:
© 2023 IUPAC & De Gruyter.
Keywords:
IUPAC Distinguished Women in Chemistry and Chemical Engineering, Women in Science, benzyl dimethyl tacn, high activity 18F, iron complex, isotopic exchange, radiofluorine, radiostabilisers, high activity F, 2023 IUPAC Distinguished Women in Chemistry and Chemical Engineering
Identifiers
Local EPrints ID: 486198
URI: http://eprints.soton.ac.uk/id/eprint/486198
ISSN: 0033-4545
PURE UUID: d7215253-8e34-4da3-8714-5db0c61e6f19
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Date deposited: 12 Jan 2024 17:45
Last modified: 02 May 2024 01:57
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Contributors
Author:
Madeleine S. Woodward
Author:
Danielle E. Runacres
Author:
Julian Grigg
Author:
Imtiaz Khan
Author:
Graeme McRobbie
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