**5. Conclusions**

Despite of promising hydrolytic stability in vitro, [18F]SiFA-Tz ([18F]**6**) demonstrated fast defluorination in vivo, after intravenous administration in CD-1 mice limiting its utility as a standalone radiotracer, for pretargeted PET imaging. However, the fluorine-18 label in the biomacromolecular radiotracer [18F]fluoroalbumin ([18F]**10**), which was radiolabeled as a proof-of-concept model compound with [18F]**6**, was found to be metabolically more stable, suggesting the utility of [18F]SiFA-Tz as a prosthetic group for in vitro radiolabeling of biomolecules of higher molecular weight. Based on these findings, the structure of [18F]SiFA-Tz warrants further optimization, before it can be considered for use as a radiolabeling tool for low molecular weight biomolecules or as a tracer for pretargeted PET imaging.

**Supplementary Materials:** The following are available online, NMR spectra, HPLC chromatograms, autoradiography profiles, and biodistributions of synthesized and radiolabeled compounds. Supplementary data are provided as a separate .pdf document.

**Author Contributions:** Conceptualization, S.O., M.S., K.H., K.W., and A.J.A.; methodology, S.O., S.I., M.S., K.H., K.W., and A.J.A.; software, S.O.; validation, S.O., S.I.; formal analysis, S.O.; investigation, S.O., S.I.; resources, M.S. and A.J.A.; data curation, S.O.; writing—original draft preparation, S.O.; writing—review and editing, S.O., S.I., M.S., K.H., K.W., and A.J.A.; visualization, S.O.; supervision, M.S., K.H., K.W., and A.J.A.; project administration, M.S. and A.J.A.; funding acquisition M.S. and A.J.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the Academy of Finland (decision numbers 306239, 298481, 278056) and a University of Helsinki three-year research grant. Open access funding provided by University of Helsinki.

**Acknowledgments:** The authors would like to thank Osku Alanen and Outi Keinänen for assistance in the experiments. The authors thank Eliza Lambidis and Petri Heinonen for the use of ESI–TOF MS and Dr. Sami Heikkinen for the use of NMR (600 MHz).

**Conflicts of Interest:** The authors declare no conflict of interest.
