The metabolic stability of these tracers is, in addition to its affinity and selectivity, an important factor for a successful disease diagnosis. PET tracers and all other drugs are subject to biotransformation which can form metabolites as a part of the inactivation or detoxification process of the human body. These metabolites may result in a higher background which has a detrimental influence on the PET image quality or can even make imaging impossible. The aim of this work was to investigate whether [18F]fluorocyclobutyl rings can be introduced into biologically active small molecules to improve metabolic stability of the PET tracer while maintaining or improving the binding affinity and lipophilicity. To test this hypothesis, the tyrosine model compound, O-(3-[18F]fluorocyclobutyl)-L-tyrosine (L-3-[18F]FCBT), was chosen to be investigated. Precursors for the indirect and direct radiolabeling as well as the non-radioactive L- and D-3-FCBT were successfully synthesized. The radiolabeled of L-3-[18F]FCBT were produced via the indirect and direct method in sufficient yield and activity for the biological evaluation. In the biological characterization, L-3-[18F]FCBT showed good tumor uptake in human lung carcinoma cell lines (A549) and was able to be blocked by both non-radioactive L-3-FCBT and non-radioactive FET. In the biodistribution study, the tracer demonstrated tumor uptake and high metabolic stability due to non accumulation of activity in bone. These results were consistent with the animal-PET imaging where L-3-[18F]FCBT showed good tumor uptake and no accumulation of activity in the bone. The D-isomer in comparison with the L-isomer was found to give lower tumor uptake and very low accumulation in the pancreas. The in vitro stability of the L-3[18F]FCBT in human and rat plasma was excellent over 120 minutes. In vivo stability in mice showed very little metabolites and L-3-[18F]FCBT is considered to be stable in vivo. These results have shown that the new [18F]fluorocyclobutyl group has the potential for the preparation of metabolically stable radiotracers and the application looks very promising.