Direct incorporation of [¹¹C]carbon dioxide for labeling bioactive molecules. An application to [¹¹C] labeled tamoxifen

Abstract

A one‐pot synthesis of [11C] labeled tamoxifen has been developed via reductive carboxylation. In this approach, [11C]CO2 is reacted with the N‐trimethylsilyl derivative of desmethyltamoxifen, followed by in situ sodium bis (2‐methoxyethoxy)aluminum hydride reduction, to afford impure [11C] labeled tamoxifen, which, on purification over a basic alumina‐silica gel column, provided pure [11C] tamoxifen in excellent radiochemical yield (65% to 84%) and radiochemical purity (>99%). The specific activity of [11C]tamoxifen was 250–400 Ci/mmol at the end of bombardment.

Silicon compounds in carbon-11 radiochemistry: present use and future perspectives

“…Upon delivery, [ 11 C]CO 2 would then be incorporated in the precursor as 11 C-silyl carbamate (15, Scheme 8) when reacted for 8 -10 minutes at 60 -65 o C. 15 is then reduced by lithium aluminium hydride to the desired tertiary 11 C-Nmethylamine with RCYs ranging between 22% and 84% (isolated, decay-corrected at EOB) and A m of 1.5 -15 GBq/µmol (calculated at EOB) within 36 -50 minutes. [52][53][54][55][56] This method was applied in the radiolabelling of a variety of tertiary alkylic amines, including the biologically-active molecules [ 11 C]tamoxifen, 53 Scheme 8 11 C-methylation of secondary amines from [ 11 C]CO 2 and trimethylsilyl amines. [52][53][54][55][56] The interaction of alkylsilyl precursors with [ 11 C]CO 2 showed to be effective in the radiosynthesis of 11 C-ureas, as well.…”

“…[52][53][54][55][56] This method was applied in the radiolabelling of a variety of tertiary alkylic amines, including the biologically-active molecules [ 11 C]tamoxifen, 53 Scheme 8 11 C-methylation of secondary amines from [ 11 C]CO 2 and trimethylsilyl amines. [52][53][54][55][56] The interaction of alkylsilyl precursors with [ 11 C]CO 2 showed to be effective in the radiosynthesis of 11 C-ureas, as well. 57 The reaction uses lithium bis(trimethylsilyl)amide (LBTMSA, Scheme 9) as a precursor which reacts with 57 The radiolabelling of 11 C-ureas could also be achieved by coupling organosilicon compounds with [ 11 C]CO.…”

“…15 is then reduced by lithium aluminium hydride to the desired tertiary 11 C- N -methylamine with RCYs ranging between 22% and 84% (isolated, decay-corrected at EOB) and A m of 1.5–15 GBq per μmol (calculated at EOB) within 36–50 minutes. 52–56 This method was applied in the radiolabelling of a variety of tertiary alkylic amines, including the biologically-active molecules [ 11 C]tamoxifen, 53 [ 11 C]imipramine, 54 [ 11 C]chlorpromazine 55 and [ 11 C]SCH 23390 ( Scheme 8 ). 56 …”

11CO2 fixation: a renaissance in PET radiochemistry

“…This work was performed by Ram and co-workers and was applied to various targets including imipramine, 36 chlorpromazine, 37 SCH-23390, 38 and tamoxifen. 39 Silanamines were prepared up to one week in advance of radiosynthesis by refluxing a secondary amine with hexamethyldisilazane (HMDS), often in the presence of catalytic quantities of ammonium sulfate. When exposed to [ 11 C]CO 2 at elevated temperatures, O -silyl carbamates were produced, which were subsequently reduced in situ by LiAlH 4 to produce labelled tertiary methylamines (Scheme 1D).…”