Oleksiy Itsenko

Labeling of aliphatic carboxylic acids using [11C]carbon monoxide.

Here we present a protocol for labeling aliphatic carboxylic acids with the positron-emitting radionuclide 11C (t1/2 = 20.4 min) at the carboxyl position using [11C]carbon monoxide via photoinitiated free radical-mediated carbonylation. A solution of an alkyl iodide in a homogenous binary organic solvent–water mixture is introduced into a high-pressure photochemical reactor containing [11C]carbon monoxide. Then the reactor contents are pressurized to 40 MPa and irradiated with ultraviolet light for 6 min. The labeled product is purified using HPLC. All manipulations with radioactivity including the labeling synthesis are carried out on an automated Synthia system. In a typical case, 3.19 GBq of purified [1-11C]1,10-decanedicarboxylic acid (with a specific radioactivity of 188 GBq/μmol) can be obtained within 35 min after the end of a 10-μAh bombardment. Compared to previous labeling methods, this protocol is compatible with a wider range of functional groups, utilizes less-sensitive precursors, and is less subject to isotopic dilution.

An evaluation of a high-pressure (11)CO carbonylation apparatus.

[(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.

An evaluation of a high-pressure11CO carbonylation apparatus: High-pressure11CO carbonylation apparatus

[(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.