Microfluidic reactions using [11C]carbon monoxide solutions for the synthesis of a positron emission tomography radiotracer

Abstract

Microfluidic technology has been used to perform [(11)C]carbonylation reactions using solutions containing [(11)C]CO in the form of the complex, copper(i)tris(3,5-dimethylpyrazolyl)borate-[(11)C]carbonyl (Cu(Tp*)[(11)C]CO). The synthesis of the model compound [(11)C]N-benzylbenzamide and the known tracer molecule [(11)C]trans-N-[5-(2-flurophenyl)-2-pyrimidinyl]-3-oxospiro[5-azaisobenzofurane-1(3H),1'-cyclohexane]-4'-carboxamide ([(11)C]MK-0233), a ligand for the neuropeptide Y Y5 receptor, have been performed using this technique. Following semi-preparative HPLC purification and reformulation, 1262 ± 113 MBq of [(11)C]MK-0233 was produced at the end of the synthesis with a specific activity of 100 ± 30 GBq μmol(-1) and a >99% radiochemical purity. This corresponds to a decay corrected radiochemical yield of 7.2 ± 0.7%. Using a 3 mL vial as the reaction vessel, and following semi-preparative HPLC purification and reformulation, 1255 ± 392 MBq of [(11)C]MK-0233 was produced at the end of the synthesis with a specific activity of 100 ± 15 GBq μmol(-1) and a >99% radiochemical purity. This corresponds to a decay corrected radiochemical yield of 7.1 ± 2.2%.

Microfluidics in Planar Microchannels: Synthesis of Chemical Compounds On-Chip

“…In fact, MCS have been successfully employed in custom adapted gas-liquid apparatuses for performing Pd-catalyzed 11 C-carbonylation reactions (Miller et al 2011). Other homogeneous 11 C-carbonylations have also been implemented in MCS, using a Cu complex as 11 C-CO source; in this case the process yield was not statistically higher, but the process resulted to be safer in terms of confinement of radioactive exhaust gases (Kealey et al 2011). 13 N is a very short half-life PET nuclide (t 1/2 ¼ 10 min) and its use is very limited due to this feature, even if it would allow a mimetic labeling of well characterized biomolecules. MCS have been used for synthesizing in flow several 13 Nnitrosothiols and 13 N-azacompounds ( Fig.…”

Nitrogen‐13: historical review and future perspectives

“…Microfluidics has been applied to the preparation of 18 F-, 73,74 11 C-, 75 and more recently 13 N-labeled compounds, 60 with promising results. Although the real application of microfluidics to the preparation of (purified) labeled compounds in sufficient quantity to approach in vivo experiments in humans needs still further development, realistic expectancies have been created, and future improvement is quite likely.…”

Microfluidic devices for radio chemical synthesis

“…Radiolabeling with 11 C can also be successfully performed with NanoTek if the radioactive precursor is dissolved in an appropriate solvent. 41 Palladiumcatalyzed incorporation of [ 11 C]-CO into the amide molecule was studied using the apparatus when the monoxide molecule was bound in a form of copper complex. The critical problem associated with the synthesis is an incorporation of [ 11 C]-CO into a urea by-product.…”