Synthesis of p-(Di-tert-butyl[18F]fluorosilyl)benzaldehyde ([18F]SiFA-A) with High Specific Activity by Isotopic Exchange: A Convenient Labeling Synthon for the 18F-Labeling of N-amino-oxy Derivatized Peptides

Abstract

The syntheses of different ¹⁸F-labeled peptides using the highly effective labeling synthon p-(di-tert-butylfluorosilyl) benzaldehyde ([¹⁸F]SiFA-A) for the development of ¹⁸F-radiopharmaceuticals for oncological positron emission tomography (PET) is reported. The novel and mild labeling technique for the radiosynthesis of [¹⁸F]SiFA-A, based on an unexpectedly efficient isotopic ¹⁹F–¹⁸F exchange, yielded the ¹⁸F-synthon [¹⁸F]SiFA-A in almost quantitative yields in high specific activities between 225 and 680 GBq/µmol (6081–18 378 Ci/mmol) without applying HPLC purification. The [¹⁸F]SiFA-A was finally used to label the N-terminal amino-oxy (N-AO) derivatized peptides AO-Tyr³-octreotate (AO-TATE), cyclo(fK(AO-N)RGD and N-AO-PEG₂-[D-Tyr-Gln-Trp-Ala-Val-βAla-His-Thi-Nle-NH₂] (AO-BZH3, a bombesin derivative) in high radiochemical yields. Density functional theory (DFT) calculations confirmed high efficiency of the isotopic exchange, which is predicted to proceed via a pentacoordinate siliconate intermediate dissociating immediately to form the radiolabeled [¹⁸F]SiFA-A.