Solutions of copper(I) tris(pyrazolyl)borate complexes have been used to greatly improve the solubility of [(11)C]carbon monoxide, enabling it to be used in low-pressure, 'one-pot' palladium-mediated carbonylation reactions to form (11)C-radiolabelled amides and ureas for use in positron emission tomography.

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%.

[(11) C]Carbon monoxide is undoubtedly a highly versatile radiolabelling synthon with many potential applications for the synthesis of positron emission tomography (PET) tracer molecules and functional groups, but why has it not found more applications in the PET radiolabelling arena? Today, (11) CO radiolabelling is still primarily viewed as a niche area; however, there are signs that this is beginning to change as some of the technical and chemistry challenges of producing, handling and reacting (11) CO are overcome. This mini review covers the more recent developments of (11) CO-labelling chemistry and is focused on palladium and rhodium-mediated carbonylation reactions that are growing in importance and finding wider application for carbon-11 PET radiotracer development.

Changes in the density of imidazoline-I 2 binding sites have been observed in a range of neurologic disorders including Alzheimer's disease, Huntington's chorea, and glial tumor; however, the precise function of these sites remains unclear. A PET probe for I 2 binding sites would further our understanding of the target and may find application as a biomarker for early disease diagnosis. Compound BU99008 has previously been identified as a promising I 2 ligand from autoradiography studies, displaying high affinity and good selectivity toward the target. In this study, BU99008 was radiolabeled with 11 C in order to image the I 2 binding sites in vivo using PET. Methods: 11 C-BU99008 was radiolabeled by N-alkylation of the desmethyl precursor using 11 C-methyl iodide. A series of PET experiments was performed to investigate the binding of 11 C-BU99008 in porcine brains, in the presence or absence of a nonradiolabeled, competing I 2 ligand, BU224. Results: 11 C-BU99008 was obtained in good yield and specific activity. In vivo, 11 C-BU99008 displayed good brain penetration and gave a heterogeneous distribution with high uptake in the thalamus and low uptake in the cortex and cerebellum. 11 C-BU99008 brain kinetics were well described by the 1-tissue-compartment model, which was used to provide estimates for the total volume of distribution (V T ) across brain regions of interest. Baseline V T values were ranked in the following order: thalamus . striatum . hippocampus . frontal cortex $ cerebellum, consistent with the known distribution and concentration of I 2 binding sites. Administration of a selective I 2 binding site ligand, BU224, reduced the V T to near-homogeneous levels in all brain regions. Conclusion: 11 C-BU99008 appears to be a suitable PET radioligand for imaging the I 2 binding sites in vivo.