Simplified one-pot <sup>18</sup>F-labeling of biomolecules with <i>in situ</i> generated fluorothiophosphate synthons in high molar activity
Hongzhang Yang, Lei Zhang, Huanhuan Liu, Yunming Zhang, Zhaobiao Mou, Xueyuan Chen, Jingchao Li, Fengming He, Zijing Li
Abstract
Rationale: Conventional 18 F-labeling methods that demand substrate pre-modification or lengthy radiosynthesis procedures have impeded the visualization and translation of numerous biomolecules, as biomarkers or ligands, using modern positron emission tomography techniques in vivo. Moreover, 18 F-labeled biomolecules in high molar activity (Am) that are indispensable for sensitive imaging could be only achieved under strict labeling conditions. Methods: Herein, 18 F-labeled fluorothiophosphate (FTP) synthons in high Am have been generated rapidly in situ in reaction solutions with < 5% water via nucleophilic substitution by wet [ 18 F]F -, which required minimal processing from cyclotron target water. Results: Various 18 F-labeled FTP synthons have been prepared in 30 sec at room temperature with high radiochemical yields > 75% (isolated, non-decay-corrected). FTP synthons with unsaturated hydrocarbon or activated ester group can conjugate with typical small molecules, peptides, proteins, and metallic nanoparticles. 337-517 GBq mol -1 Am has been achieved for 18 F-labeled c(RGDyK) peptide using an automatic module with 37-74 GBq initial activity.