F on: Fluorotriorganosilyl‐derivatized Tyr3‐octreotate was labeled with 18F− providing the first practical formulation in 18F‐radiochemistry for the labeling of a peptide (see scheme). The very mild reaction conditions and the fast labeling make this strategy a valuable tool for the synthesis of 18F‐radiopharmaceuticals.

The syntheses of different (18)F-labeled peptides using the highly effective labeling synthon p-(di- tert-butylfluorosilyl) benzaldehyde ([ (18)F]SiFA-A) for the development of (18)F-radiopharmaceuticals for oncological positron emission tomography (PET) is reported. The novel and mild labeling technique for the radiosynthesis of [ (18)F]SiFA-A, based on an unexpectedly efficient isotopic (19)F- (18)F exchange, yielded the (18)F-synthon [ (18)F]SiFA-A in almost quantitative yields in high specific activities between 225 and 680 GBq/micromol (6081-18 378 Ci/mmol) without applying HPLC purification. The [ (18)F]SiFA-A was finally used to label the N-terminal amino-oxy (N-AO) derivatized peptides AO-Tyr (3)-octreotate (AO-TATE), cyclo(fK(AO-N)RGD and N-AO-PEG 2-[D-Tyr-Gln-Trp-Ala-Val-betaAla-His-Thi-Nle-NH 2] (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 [ (18)F]SiFA-A.

In this short review we describe recent methods and novel trends for the introduction of fluorine-18 into molecules which in turn are intended to serve as imaging agents for the in vivo imaging modality positron emission tomography (PET). These 18 F-labeling schemes are based on enzymatic fluorination, the use of ionic liquids, protic solvents acting as catalysts, application of "click chemistry", thiol-reactive labeling agents for peptide and protein labeling and the most recent introduction of "non-classical" radiochemistry based on organo-phosphorous, organo-boron and organo-silicon radiochemistry. The latter approach for the first time introduced an 18 F-chemistry characterized by high selectivity and unique efficiency making complicated work-up procedures obsolete.