An evaluation of a high‐pressure ¹¹CO carbonylation apparatus

Abstract

[(11)C]Carbon monoxide ((11)CO) is a versatile building block for the synthesis of Positron Emission Tomography (PET) radioligands. However, the difficulty of trapping (11)CO in a small solvent volume has limited its utility. We here report an evaluation of a simple, fully automated high-pressure synthesizer prototype for the use in (11)C-carbonylation reactions. [(11)C]Carbon monoxide was easily prepared by online reduction of [(11)C]carbon dioxide using either Mo(s) or Zn(s) as the reducing agent. The conversion yield of (11)CO was >99% when zinc was used as the reducing agent, and the corresponding value for Mo was approximately 71%. When the Zn or Mo column was constantly kept under inert atmosphere, no significant decrease in reducing properties was observed for more than 100 (11)CO productions. However, in our hands, Mo reductant was much easier to service. A total of nine functional groups were successfully radiolabeled using the (11)CO synthesizer prototype. All measured radiochemical yields exceeded 37%, and the (11)CO trapping efficiency was generally above 90%, except for the Suzuki coupling where the trapping efficiency was 80%. This high-pressure synthesizer using [(11)C]carbon monoxide as the labeling precursor is easy to operate allowing for (11)C-carbonylation reactions to be performed in a high yield and in a routinely fashion.

Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging

“…[ 11 C]Carbon monoxide may be produced on-line in high yield by passage of [ 11 C]carbon dioxide over heated zinc [337] or molybdenum [337, 338]. A major obstacle to the early application of [ 11 C]carbon monoxide to producing radiotracers was its low solubility in organic solvents.…”

Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry

“…[ 11 C]Carbon monoxide ([ 11 C]CO) was one of the first 11 C‐tracers used for blood volume measurements in humans . [ 11 C]CO is generally produced by the gas‐phase reduction of cyclotron‐produced [ 11 C]CO 2 on a metal surface (zinc or molybdenum) placed in a heated quartz tube at high temperatures, Scheme …”

“…Methods for the reduction of [ 11 C]CO 2 using zinc ovens often suffer from the degradation of the metal surface by formation of zinc oxides over a few [ 11 C]CO production cycles. Zinc columns require frequent changes, cleaning, and careful pre‐purification of the [ 11 C]CO 2 in order to assure reproducible [ 11 C]CO yields . In addition, the melting point of zinc (420°C) is close to the temperature required for the [ 11 C]CO 2 reduction to occur (400°C).…”

“…The use of molybdenum as a reducing metal in high‐pressure systems has recently shown more reproducible [ 11 C]CO yields compared with the zinc method . Molybdenum is known to readily react with [ 11 C]CO 2 to form [ 11 C]CO and molybdenum oxide with a maximum efficiency at 850°C .…”

“…The latter has also shown reducing properties towards [ 11 C]CO 2 yielding [ 11 C]CO, which might improve the performance of the system and avoid repeated maintenance . This methodology enables the production of [ 11 C]CO in yields of up to 70% over several production cycles . In addition, the high melting point of this metal (>>850°C) avoids the risk of catalyst melting during the conversion process.…”