A Novel Method for Direct Site-Specific Radiolabeling of Peptides Using [18F]FDG

We have used the well-accepted and easily available 2-[F-18]fluoro-2-deoxyglucose ([F-18]FDG) positron emission tomography (PET) tracer as a prosthetic group for synthesis of F-18-labeled peptides. We herein report the synthesis of [F-18]FDG-RGD (F-18 labeled linear RGD) and [F-18]FDG-cyclo(RGD(D)YK) (F-18 labeled cyclic RGD) as examples of the use of [F-18]FDG. We have successfully prepared [F-18]FDG-RGD and [F-18]FDG-cyclo(RGD(D)YK) in 27.5% and 41% radiochemical yields (decay corrected) respectively. The receptor binding affinity study of FDGcyclo(RG(D)YK) for integrin alpha(v)beta(3) using alpha(v)beta(3) Positive U87MG cells confirmed a competitive displacement with 121 I-echistatin as a radioligand. The IC50 value for FDG-cyclo(RG(D)YK) was determined to be 0.67 +/- 0.19 mu M. High-contrast small animal PET images with relatively moderate tumor uptake were observed for [F-18]FDG-RGD and [F-18]FDG-cyclo(RG(D)DYK) as PET probes in xenograft models expressing alpha(v)beta(3) integrin. In conclusion, we have successfully used [F-18]FDG as a prosthetic group to prepare 18F]FDG-RGD and [F-18]FDG-cyclic[RGD(D)YK] based on a simple one-step radiosynthesis. The one-step radiosynthesis methodology consists of chemoselective oxime formation between an aminooxy-functionalized peptide and [F-18]FDG. The results have implications for radiolabeling of other macromolecules and would lead to a very simple strategy for routine preclinical and clinical use.