CycloSiFA: The Next Generation of Silicon-Based Fluoride Acceptors for Positron Emission Tomography (PET)

The ring-opening Si-fluorination of a variety of azasilole derivatives cyclo-1-(iPr₂ Si)-4-X-C₆ H₃ -2-CH₂ NR (4: R=2,6-iPr₂ C₆ H₃ , X=H; 4 a: R=2,4,6-Me₃ C₆ H₂ , X=H; 9: R=2,6-iPr₂ C₆ H₃ , X=tBuMe₂ SiO; 10: R=2,6-iPr₂ C₆ H₃ , X=OH; 13: R=2,6-iPr₂ C₆ H₃ , X=HCCCH₂ O; 22: R=2,6-iPr₂ C₆ H₃ , X=tBuMe₂ SiCH₂ O) with different ¹⁹ F-fluoride sources was studied, optimized and the experience gained was used in a translational approach to create a straightforward ¹⁸ F-labelling protocol for the azasilole derivatives [¹⁸ F]6 and [¹⁸ F]14. The latter constitutes a potential clickable CycloSiFA prosthetic group which might be used in PET tracer development using Cu-catalysed triazole formation. Based on our findings, CycloSiFA has the potential to become a new entry into non-canonical labelling methodologies for radioactive PET tracer development.