Bifunctional Hexadentate Pyclen-Based Chelating Agent for Mild Radiofluorination in Aqueous Solution at Room...

Positron Emission Tomography (PET) is used in oncology for tumor diagnosis, commonly relying on fluorine-18 (¹⁸F) emission detection. The conventional method of ¹⁸F incorporation on to probes by covalent bonding is harsh for sensitive biomolecules, which are nonetheless compounds of choice for the development of targeted probes. This study explores gallium-¹⁸F (Ga¹⁸F) coordination, a milder alternative method occurring in aqueous media at the final stage of radiosyntheses. Pyclen-based chelating agents were proposed to capture (GaF) species at room temperature and pH≥5 making the radiofluorination process compatible with heat- and acid-sensitive biomolecules. Highly promising results were obtained with the PC2A-based chelating agent LH₂ derived from the new bifunctional PC2A-OAE-NCS compound. The solid-state structure of GaF(L) was elucidated by X-ray diffraction and revealed an unconventional heptacoordination of Ga(III). A high radiochemical conversion (RCC) of 86 % was achieved at room temperature, in water at pH 5 within 20 minutes. Stability studies showed the robustness of the GaF(L) complex in aqueous media for at least one day and at least one hour for the radiolabeled analog Ga¹⁸F(L). These findings demonstrated that PC2A-based compounds are chelating agents of choice for (Ga¹⁸F) species, suggesting a real technological breakthrough for PET imaging and precision medicine.