## 2 Basics of Silicon-\({}^{18}\)F Radiochemistry  
Up until recently, only sporadic attempts to bind \({}^{18}\)F to a different atom other than carbon have been reported in the literature. One reason might be that for many years, mainly small radiolabeled compounds were in the focus of \({}^{18}\)F labeling chemistry for PET imaging. Those small compounds are most of the time not amenable to heteroatomic modifications because of their sensitive nature and their very specific structure-related target binding. Only a few years ago, radiochemists started to use \({}^{18}\)F to label even complex molecules, such as peptides and proteins. Even today, the \({}^{18}\)F labeling of these compounds of high molecular weight is challenging, and requires elaborate pathways to introduce the radionuclide. Direct labeling approaches for peptides based on C-\({}^{18}\)F bond formation are rare and not universally applicable. Thus, so-called prosthetic labeling sythons, already bearing the \({}^{18}\)F atom (attached to a carbon), have to be employed which is even more important in the case of proteins, bearing a multitude of different functional groups. It seems that C-\({}^{18}\)F radiochemistry has reached its limits and alternative strategies have to be found to advance the field further in terms of convenience, applicability and reliability. The use of Si-F bond formation in radiochemistry dates back to 1958 [19] and a few more papers on that subject have been published before the first _in vivo_ application was reported [20; 21; 22]. At first glance, the use of silicon for binding \({}^{18}\)F appears not to be a promising choice. Despite the fact that the bond energy of the Si-F bond is _ca._ 90 kJ higher than that of the C-F bond (570 kJ\(\cdot\)mol\({}^{-1}\)_vs._ 480 kJ\(\cdot\)mol\({}^{-1}\)), the kinetic stability of the Si-F bond against hydrolysis is very low due to strong bond polarization. This is an apparent obstacle for the use of Si-\({}^{18}\)F bearing compounds as potential tracer probes for PET, since under physiological conditions present in the blood, the Si-\({}^{18}\)F bond would undergo immediate hydrolysis, resulting in the detachment of the \({}^{18}\)F from the biomolecule. This was proved to be true in 1985 by [PERSON] and co-workers [23], who labeled a simple compound like chlorotrimethylsilane with anionic \({}^{18}\)F\({}^{-}\) in good radiochemical yields of 65% in one step. The resulting [\({}^{18}\)F]fluorotrimethylsilane is a volatile compound which was shown to be quickly taken up in the bloodstream when inhaled by rats. It quickly turned out that the _in vivo_ stability of the Si-\({}^{18}\)F bond was rather low and the corresponding silanole was more or less formed immediately, resulting in the predominant uptake of \({}^{18}\)F\({}^{-}\) into the bones, forming fluoroapatite. Even back in 1985, the authors already suggested the use of bulkier substituents on the Si atom to shield the Si-F bond from hydrolysis. Interestingly, [PERSON] described a purification method for \({}^{18}\)F\({}^{-}\) using [\({}^{18}\)F]fluorotrimethylsilane, exploiting the easy hydrolysis of the Si-\({}^{18}\)F bond in nearly anhydrous acetonitrile to form highly nucleophilic \({}^{18}\)F\({}^{-}\) a few years later [24]. This is the first example in the literature where highly nucleophilic \({}^{18}\)F\({}^{-}\) was prepared without azeotropic water removal, which was then used in the synthesis of [\({}^{18}\)F]2-fluoro-2-deoxy-D-glucose (FDG), the most prominent \({}^{18}\)F-radiotracer to date [25]. The need of bulky substituents at the Si atom was reiterated later by [PERSON] _et al._[26]. They suggested the use of alkoxy silanes as potential precursor compounds for the \({}^{18}\)F-labeling with aqueous HF, actually a reaction already well known to organic chemists for the deprotection of silylated alcohols.