title: A novel method for direct site-specific radiolabeling of peptides using [18F]FDG.
abstract: We have used the well-accepted and easily available 2-[(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) positron emission tomography (PET) tracer as a prosthetic group for synthesis of (18)F-labeled peptides. We herein report the synthesis of [(18)F]FDG-RGD ((18)F labeled linear RGD) and [(18)F]FDG-cyclo(RGD(D)YK) ((18)F labeled cyclic RGD) as examples of the use of [(18)F]FDG. We have successfully prepared [(18)F]FDG-RGD and [(18)F]FDG-cyclo(RGD(D)YK) in 27.5% and 41% radiochemical yields (decay corrected) respectively. The receptor binding affinity study of FDG-cyclo(RGD(D)YK) for integrin alpha(v)beta(3), using alpha(v)beta(3) positive U87MG cells confirmed a competitive displacement with (125)I-echistatin as a radioligand. The IC(50) value for FDG-cyclo(RGD(D)YK) was determined to be 0.67 +/- 0.19 muM. High-contrast small animal PET images with relatively moderate tumor uptake were observed for [(18)F]FDG-RGD and [(18)F]FDG-cyclo(RGD(D)YK) as PET probes in xenograft models expressing alpha(v)beta(3) integrin. In conclusion, we have successfully used [(18)F]FDG as a prosthetic group to prepare (18)F]FDG-RGD and [(18)F]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 [(18)F]FDG. The results have implications for radiolabeling of other macromolecules and would lead to a very simple strategy for routine preclinical and clinical use.
authors.affiliation: Molecular Imaging Program at Stanford, Departments of Radiology and Bioengineering, Bio-X Program, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Namavari
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Abhijit
authors.initials: A
authors.lastname: De
authors.forename: Jelena
authors.initials: J
authors.lastname: Levi
authors.forename: Joshua K
authors.initials: JK
authors.lastname: Hoerner
authors.forename: Shahriar S
authors.initials: SS
authors.lastname: Yaghoubi
authors.forename: Faisal A
authors.initials: FA
authors.lastname: Syud
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid