High molar activity [11C]phosgene from [11C]CO2

[ 11 C]Phosgene is a known but underutilised labelling synthon in PET-tracer development. The production of [ 11 C]phosgene faces many problems such as difficulties in achieving high molar activity, regular key component replacement and complexity of the synthesis, thereby hindering its wider use. In this paper, a robust and semi-automated synthesis route for production of [ 11 C]phosgene from [ 11 C]CO 2 was developed to solve issues restricting the use of [ 11 C]phosgene. The high molar activity [ 11 C]phosgene was then used for the labelling of biologically important molecules as a proof of concept. [ 11 C]Phosgene was synthesized from [ 11 C]CO by UV-mediated photochemical chlorination with chlorine gas. [ 11 C]CO was produced by the fluoride-activated disilane reduction of cyclotron-produced [ 11 C]CO 2 . [ 11 C]Phosgene was produced with satisfactory radiochemical yield (13 ± 1 GBq at EOS, 30 ± 4% dc. to SOS) based on [ 11 C]CO 2 and molar activity of 249 ± 40 GBq/µmol at EOS (n = 3). The radiosynthesis time was approximately 20 min. A robust synthesis route for production of high molar activity [ 11 C]phosgene from [ 11 C]CO 2 was developed. The simplicity and mild reaction conditions of the [ 11 C]CO production method used eliminate the previous issues with Zn-based reduction of [ 11 C]CO 2 . Intermediate purification of [ 11 C]CO guaranteed efficient [ 11 C]phosgene production, and removal of unreacted Cl 2 minimised unwanted side reactions. This method utilises a fixed-line device with simple set up and mild conditions. With this method, it is possible to perform syntheses reliably with good radiochemical yields and high molar activities in a short synthesis time.

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Journal
EJNMMI Radiopharmacy and Chemistry
Published
2026-07-24
DOI
https://doi.org/10.1186/s41181-026-00472-w
Primary Topic
Radiopharmaceutical Chemistry and Applications
Type
article
Field-Weighted Citation Impact
0.00

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article

High molar activity [11C]phosgene from [11C]CO2

Johan Rajander, Anna Krzyczmonik, Olof Solin, Simo Salo et al.
EJNMMI Radiopharmacy and Chemistry
Radiopharmaceutical Chemistry and Applications
article

High molar activity [11C]phosgene from [11C]CO2

Johan Rajander, Anna Krzyczmonik, Olof Solin, Simo Salo, Edla Kerminen, Anna K. Kirjavainen, Thomas Keller
article en

Abstract

[ 11 C]Phosgene is a known but underutilised labelling synthon in PET-tracer development. The production of [ 11 C]phosgene faces many problems such as difficulties in achieving high molar activity, regular key component replacement and complexity of the synthesis, thereby hindering its wider use. In this paper, a robust and semi-automated synthesis route for production of [ 11 C]phosgene from [ 11 C]CO 2 was developed to solve issues restricting the use of [ 11 C]phosgene. The high molar activity [ 11 C]phosgene was then used for the labelling of biologically important molecules as a proof of concept. [ 11 C]Phosgene was synthesized from [ 11 C]CO by UV-mediated photochemical chlorination with chlorine gas. [ 11 C]CO was produced by the fluoride-activated disilane reduction of cyclotron-produced [ 11 C]CO 2 . [ 11 C]Phosgene was produced with satisfactory radiochemical yield (13 ± 1 GBq at EOS, 30 ± 4% dc. to SOS) based on [ 11 C]CO 2 and molar activity of 249 ± 40 GBq/µmol at EOS (n = 3). The radiosynthesis time was approximately 20 min. A robust synthesis route for production of high molar activity [ 11 C]phosgene from [ 11 C]CO 2 was developed. The simplicity and mild reaction conditions of the [ 11 C]CO production method used eliminate the previous issues with Zn-based reduction of [ 11 C]CO 2 . Intermediate purification of [ 11 C]CO guaranteed efficient [ 11 C]phosgene production, and removal of unreacted Cl 2 minimised unwanted side reactions. This method utilises a fixed-line device with simple set up and mild conditions. With this method, it is possible to perform syntheses reliably with good radiochemical yields and high molar activities in a short synthesis time.

EJNMMI Radiopharmacy and Chemistry
Åbo Akademi University (FI), University of Turku (FI), National Centre for Nuclear Research (PL), Turku PET Centre (FI)
Luonnontieteiden ja Tekniikan Tutkimuksen Toimikunta
Openalex Percentile: Top 9%
Radiopharmaceutical Chemistry and Applications
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