Labeling biomolecules with ¹⁸F is usually done through coupling with prosthetic groups, which requires several time-consuming radiosynthesis steps and therefore in low labeling yield. In this study, we designed a simple one-step ¹⁸F-labeling strategy to replace the conventional complex and the long process of multiple-step radiolabeling procedure. Both monomeric and dimeric
cyclic RGD peptides were modified to contain 4-NO₂-3-CF₃ arene as precursors for direct ¹⁸F labeling. Binding of the two functionalized
peptides to
integrin α(v)β₃ was tested in vitro using the MDA-MB-435 human breast cell line. The most promising functionalized
peptide, the dimeric
cyclic RGD, was further evaluated in vivo in an orthotopic MDA-MB-435
tumor xenograft model. The use of relatively low amount of precursor (~0.5 μmol) gave reasonable yield, ranging from 7 to 23% (decay corrected, calculated from the start of synthesis) after HPLC purification. Overall reaction time was 40 min, and the specific activity of the labeled
peptide was high. Modification of RGD
peptides did not significantly change the biological binding affinities of the modified
peptides. Small animal PET and biodistribution studies revealed
integrin specific
tumor uptake and favorable biokinetics. We have developed a novel one-step ¹⁸F radiolabeling strategy for
peptides that contain a specific arene group, which shortens reaction time and labor significantly, requires low amount of precursor, and results in specific activity of 79 ± 13 GBq/μmol. Successful introduction of 4-fluoro-3-trifluoromethylbenzamide into RGD
peptides may be a general strategy applicable to other biologically active
peptides and
proteins.