Introduction: The carbonyl group is the most widespred functional groups, presenting in many bioactive molecules. That makes the [¹¹C]carbon monoxide an attractive precursor for labeling a wide range of drug molecules. However, ¹¹C-carbonylation remains challenging due to the low reactivity and poor solubility of CO. We report here a highly efficient and fully automated method using commercially available GE TracerLab FXM or FXC suitable for cGMP production of radiopharmaceuticals.
Methods: Production of [¹¹C]CO: Method A: [¹¹C]CO₂was passed through a charcoal column (950 ^oC) at flow rates of 50, 250, and 600 mL/min. Method B: [¹¹C]CO₂was passed through a molybdenum column (850 ^oC) at flow rates of 35, 50, and 60 mL/min. In loop ¹¹C-carbonylation: The investigation was started with [¹¹C]N-benzyl benzamide, followed by several drug molecules. Pd₂(π-cinnamyl)Cl₂ or Pd(dba)₂ and XantPhos or N-XantPhos were dissolved into THF and mixed with organohalide, followed by an amine. The mixture was loaded onto a HPLC loop. The produced [11C]CO was trapped in a silica column immersed in liquid N2 and then released into the HPLC loop. The loop was sealed for 5 mins at rt. The reaction mixture was purified by semi-preparative HPLC.
Results: The yields of [¹¹C]CO were 85-93% and 65-75% at various flow rates from method A and B, respectively. Both palladium catalysts gave comparable yields, but Pd(dba)2 and N-XantPhos were more soluble in THF. Several drug molecules have been labeled with radiochemical yields of 3.8-7.2% (non-corrected) and purities of 90-98%. Molar activities were < 0.1 Ci/µmol and > 5 Ci/µmol from the charcoal and molybdenum methods, respectively.
Conclusions: We have developed a simple and high yield ¹¹C-carbonyl labeling process. The ¹¹C-carbonylation was carried out at room temperature and no high pressure or high temperature equipment is required. The qualification of PET tracers produced with this method for clinical application is under way.

Karim Mhanna

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