## 7 Silicon Building Blocks Containing H, OH and Alkoxy moieties as Leaving Groups
Important advantages of this procedure are the mild labeling conditions applied which result in the formation of only one radiolabeled product, making an HPLC purification dispensable. However, in the first attempts of peptide labeling using this strategy, the achieved specific activities (SAs) of the labeled peptides were rather low (between 3-5 GBq/umol) even when testing different reaction conditions. This resulted in the development of a two-step labeling approach in order to achieve higher specific activities which consisted of _i_) the \({}^{18}\)F-radioling of SiFA-derivatized aldehyde (**3**) under mild conditions in high RCYs of up to 97% and high SAs of 225-680 GBq/umol and _ii_) the subsequent chemo- and regioselective conjugation of the obtained aldehyde to different aminooxy-functionalized peptides [30]. The second step also proceeded efficiently and gave the products in short overall synthesis times of 40 min, comparably high specific activities and overall RCYs of 50-55% after HPLC purification. Using this experimental setup, Tyr\({}^{3}\)-octreotate, cRGD and BZH3, which have gained widespread interest in clinical imaging of different malignant diseases, could be radiolabeled with \({}^{18}\)F (Figure 9). Furthermore, this approach has the advantage of being applicable to the \({}^{18}\)F-labeling of various aminooxy-derivatized peptides. In order to circumvent a two-step labeling reaction requiring a final HPLC purification which reduces the convenience and lengthens the preparation time (despite the fast reaction kinetics of the SiFA approach), optimized labeling conditions were developed. These allow for an efficient reaction at room temperature yielding the product within 30 min in high RCYs of 38% after purification and specific activities between 29 and 56 GBq/\(\upmu\)mol, which is sufficient for receptor imaging _in vivo_. The key to these favorable results is the use of very small nanomolar amounts of the respective \({}^{19}\)F-labeling precursors (10 to 25 nmol) [38]. In order to allow for a more modular synthesis of SiFA-peptides, enabling not only a terminal but also an intra-sequential introduction of the SiFA building block, a SiFA-containing amino acid derivative (**15**) was developed and shown to be useful for the intra-sequential SiFA-derivatization as demonstrated on the standard Fmoc-based SPPS of three model Tyr\({}^{3}\)-octreotate derivatives [39]. In later studies, when comparing the substitution pattern on the silicon atom with regard to radiolabeling efficiency and hydrolytic stability, an investigation was mounted to see if silicon moieties containing substituents sterically, not as demanding as _tert_-butyl groups, could be used--in order to achieve a high incorporation rate of \({}^{18}\)F into the silicon building block by substitution of H-, OH- and alkoxy-residues [29, 33, 40, 41] Although it was found that, in general, the silicon moieties comprising smaller substituents on the silicon atom exhibited a higher isotopic exchange efficiency than the corresponding bulky _tert_-butyl-containing ones [29, 33], it was also shown that the hydrolytic stability of the _tert_-butyl substituted building blocks was by far the highest [29, 40]. This effect of limited hydrolytic stability was also observed in the case of the corresponding model peptides [29, 41] and bombesin derivatives [40] modified with isopropyl-containing silicon building blocks. With regard to \({}^{18}\)F-labeling, relatively high amounts of precursor (e.g., alkoxyl-silanes) had to be used. [PERSON] co-workers needed 6 mg (11 umol) of a small model peptide derivatized with an alkoxyl-silane moiety (Figure 10) [41]. Of course, the use of such high amounts of precursor peptides necessitates a final HPLC purification of the \({}^{18}\)F-labeled peptide. Of crucial importance are, not only the used labeling conditions, achievable RCYs and specific activities, but also the _in vivo_ behavior of the \({}^{18}\)F-labeled peptides that were obtained. In a study carried out by [PERSON] _et al_.