Abstract View

Introduction: Bioactive benzophenones exhibit diverse biological properties, including antimicrobial activity, strong antioxidant activity, and notable anticancer actions. However, labelling benzophenones with ¹¹C using[¹¹C]carbon monoxide is challenging and requires special equipment. Building on the success of the in-loop method at the University of Michigan, ^1-4 we report here radiosynthesis of 19 aryl [¹¹C]-ketones using commercially available GE TracerLab FX upon slight modifications. The simple and easy modification can be adopted to FXc or FXn synthesis modules and enables cGMP production of various radiopharmaceuticals. 

Methods: In loop ¹¹C-carbonylation for aryl [¹¹C]-ketones: [¹¹C]CO₂ was passed through a heated molybdenum column (850 °C) under a helium flow of 50 mL/min. The resulting [¹¹C]CO was trapped on a silica column immersed in liquid nitrogen at −78 °C. Pd(dba)₂ and P(t-Bu)₃ were dissolved in THF and mixed with the organoiodide precursor. The reaction mixture was stirred at room temperature for 5 min, after which the organotin precursor dissolved in 1,4-dioxane was added. Five minutes prior to the end of bombardment, the reaction mixture was loaded into an HPLC loop. Following this, the [¹¹C]CO trap was removed from liquid nitrogen to release [¹¹C]CO into the HPLC loop. The loop was sealed at ambient pressure and heated in an oil bath at 120–140 °C for 10 min. The reaction mixture was then flushed from the HPLC loop with THF and transferred into a dose vial for subsequent analytical HPLC analysis (Scheme 1). 

Scheme 1: Synthesis of aryl [¹¹C]-ketones.

Results: The radiochemical conversions for aryl [¹¹C]-ketones were in 11–84% as determined by analytical HPLC. [¹¹C]Oxybenzone was produced in decay corrected RCY of 2.94 ± 2.5% (1.02 ±  0.86% non-decay corrected RCY based upon ~1.1 Ci or 2.2 Ci of starting ¹¹CO, of 15 min or 30 min, n = 2). Furthermore, the molar activity was 19.4 ± 5.88 GBq/µmol (523.4 ± 159 mCi/µmol), and the product was obtained in 96.5 ±  0.49% radiochemical purity.

Conclusions: We have developed a straightforward method for the [¹¹C]-labeling of aryl [¹¹C]-ketones using commercially available radiosynthesis modules (GE TRACERlab FXs), following minor modifications. These modules are widely used for cGMP production of radiopharmaceuticals, and the method does not require high-pressure conditions.

References: 1). D. J. Donnelly, S. Preshlock, T. Kaur, P. J. H. Scott, X. Shao, Front. Nucl. Med. 2022, 1, 820235; 2). T. Kaur, X. Shao, M. S. Sanford, P. J. H. Scott, Org. Process Res. Dev. 2023, 27, 373−381; 3). T. Kaur, J. S. Wright, J. Godinez, X. Shao, P. J. H. Scott, J. Label. Compd. Radiopharm.,  2023, 1- 10; 4) T. Kaur, A. Brooks, X. Shao, P. J. H. Scott, Asian J. Org. Chem. 2025, 14, e202500121.

Acknowledgements: This work was supported by the NIH [Award Number R01EB021155 (P.J.H.S.)]. The University of Michigan (Department of Radiology and SOAR) are also duly acknowledged for financial support of this work.