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

Abstract

Here we present a protocol for labeling aliphatic carboxylic acids with the positron-emitting radionuclide 11C (t(1/2) = 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-(11)C]1,10-decanedicarboxylic acid (with a specific radioactivity of 188 GBq/micromol) can be obtained within 35 min after the end of a 10-microAh 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.

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

“…Because of the ubiquity of the C═O functional group in many biologically active molecules, the chemical versatility of CO and the potential of palladium‐promoted carbonylation cross‐coupling reactions have made [ 11 C]CO an attractive tool for the development of 11 C‐chemistry methodologies. To date, [ 11 C]CO has been used for direct 11 C‐carbonylation reactions producing a vast range of 11 C‐compounds, such as [ 11 C]amides, [ 11 C]ureas, [ 11 C]carboxylic acids, and [ 11 C]esters, Scheme . Compared with traditional chemical methods, a major challenge in radiochemistry is the reaction stoichiometry, because in radiochemistry the amount of 11 C produced is generally in the nano‐picomolar range (10 −9 –10 −12 mol).…”

“…To date, [ 11 C]CO has been used for direct 11 C-carbonylation reactions producing a vast range of 11 Ccompounds, such as [ 11 C]amides, [ 11 C]ureas, [ 11 C]carboxylic acids, and [ 11 C]esters, Scheme 13. 34,55,57,59,[61][62][63][64][65][66][67][68][69][70][71][72] Compared with traditional chemical methods, a major challenge in radiochemistry is the reaction stoichiometry, because in radiochemistry the amount of 11 C produced is generally in the nano-picomolar range (10 −9 -10 −12 mol). Even "low levels" of impurities in the reagents and solvents used may be present in excess compared with the radiolabelled starting material.…”

[Carboxyl‐11C]Labelling of Four High‐Affinity cPLA2α Inhibitors and Their Evaluation as Radioligands in Mice by Positron Emission Tomography

“…[25][26][27][28] However,s ome methods suffer drawbacks, such as reagenta ir/moisture sensitivity, [26] requirement to use high amountso fp recursor, [25] or low molar activity. [29] [ 11 C]Carbon monoxide has been gaining importance as au seful primary labellinga gent because:1 )itc an be synthesized by passage of cyclotron-produced[ 11 C]carbon dioxide over heated molybdenum (875 8C) in high yield and high molara ctivity; [30] 2) new apparatus [31][32][33][34][35][36] and techniques [37][38][39][40][41] have been developed for increasing [ 11 C]carbon monoxide availability in small volumes of organic solvents;a nd 3) new methods fort he transition-metal-mediated insertions of [ 11 C]carbon monoxide into radiotracers [42][43][44][45][46][47] have expandedt he choice of reagents and functional group tolerance. We chose to explore the Pd 0 -mediated [ 11 C]carbon monoxide insertion in iodo precursorsf or the labellingo f1-4 because this method requires low amounts of iodo precursors that should be stable and air-insensitive, and because the methodi se xpected to show high functional group tolerance.…”

Specific Activity of 11C-Labelled Radiotracers: A Big Challenge for PET Chemists

“…Thus, Grignard-type reactions to yield [carbonyl-11 C]carboxylates can be carried out by using directly cyclotron generated [ 11 C]CO 2 ; the latter can be also converted into [ 11 C]CO through the reduction over zinc or molybdenum in an on-line process and further used to produce (e.g. via the palladium-mediated [ 11 C]carbonylation of olefins, alkynes and organic halides) carboxylic acids (Itsenko et al, 2006), amides (Rahman et al, 2003) and imides (Karimi et al, 2001), among others. [ 11 C]CO 2 can be also transformed into [ 11 C]CH 3 OH via reduction with LiAlH 4 ; the latter can be further reacted with hydriodic acid to yield [ 11 C]CH 3 I which is by far the most commonly used radioactive precursor for introducing Carbon-11 into organic molecules via nucleophilic substitution using amines (Mathis et al, 2003), amides (Hashimoto et al, 1989), phenols (Ehrin et al, 1985) or thiol groups (Langstrom & Lundqvist, 1976).…”