Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups

Bioconjug Chem. 2008 Apr;19(4):951-7. doi: 10.1021/bc700472w. Epub 2008 Mar 15.


Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the (18)F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [(18)F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [(18)F]5, and [(18)F]-4-(3-fluoropropoxy)benzaldehyde, [(18)F]9, in addition to the widely used 4-[(18)F]fluorobenzaldehyde, [(18)F]12. The three (18)F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [(18)F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [(18)F]10 or [(18)F]13. The radioactivity from the [(18)F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [(18)F]10 and [(18)F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [(18)F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate.

MeSH terms

  • Aldehydes / chemistry*
  • Animals
  • Binding, Competitive
  • Carcinoma, Lewis Lung / diagnostic imaging
  • Cell Line, Tumor
  • Fluorine Radioisotopes
  • Hydrophobic and Hydrophilic Interactions
  • Integrins / metabolism
  • Mice
  • Neovascularization, Pathologic / diagnostic imaging
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacokinetics*
  • Polyethylene Glycols / chemistry
  • Positron-Emission Tomography


  • Aldehydes
  • Fluorine Radioisotopes
  • Integrins
  • Peptides, Cyclic
  • cyclic arginine-glycine-aspartic acid peptide
  • Polyethylene Glycols