MicroPET imaging of brain tumor angiogenesis with 18F-labeled PEGylated RGD peptide

Eur J Nucl Med Mol Imaging. 2004 Aug;31(8):1081-9. doi: 10.1007/s00259-003-1452-2. Epub 2004 Apr 29.


We have previously labeled cyclic RGD peptide c(RGDyK) with fluorine-18 through conjugation labeling via a prosthetic 4-[18F]fluorobenzoyl moiety and applied this [18F]FB-RGD radiotracer for alphav-integrin expression imaging in different preclinical tumor models with good tumor-to-background contrast. However, the unfavorable hepatobiliary excretion and rapid tumor washout rate of this tracer limit its potential clinical applications. The aims of this study were to modify the [18F]FB-RGD tracer by inserting a heterobifunctional poly(ethylene glycol) (PEG, M.W. =3,400) between the 18F radiolabel and the RGD moiety and to test this [18F]FB-PEG-RGD tracer for brain tumor targeting and in vivo kinetics. [18F]FB-PEG-RGD was prepared by coupling the RGD-PEG conjugate with N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) under slightly basic conditions (pH=8.5). The radiochemical yield was about 20-30% based on the active ester [18F]SFB, and specific activity was over 100 GBq/micromol. This tracer had fast blood clearance, rapid and high tumor uptake in the subcutaneous U87MG glioblastoma model (5.2+/-0.5%ID/g at 30 min p.i.). Moderately rapid tumor washout was observed, with the activity accumulation decreased to 2.2+/-0.4%ID/g at 4 h p.i. MicroPET and autoradiography imaging showed a very high tumor-to-background ratio and limited activity accumulation in the liver, kidneys and intestinal tracts. U87MG tumor implanted into the mouse forebrain was well visualized with [18F]FB-PEG-RGD. Although uptake in the orthotopic tumor was significantly lower (P<0.01) than in the subcutaneous tumor, the maximum tumor-to-brain ratio still reached 5.0+/-0.6 due to low normal brain background. The results of H&E staining post mortem agreed with the anatomical information obtained from non-invasive microPET imaging. In conclusion, PEGylation suitably modifies the physiological behavior of the RGD peptide. [18F]FB-PEG-RGD gave improved tumor retention and in vivo kinetics compared with [18F]FB-RGD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / metabolism*
  • Female
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / metabolism*
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Neovascularization, Pathologic / diagnostic imaging*
  • Neovascularization, Pathologic / metabolism*
  • Organ Specificity
  • Peptides, Cyclic / pharmacokinetics*
  • Polyethylene Glycols / pharmacokinetics*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution
  • Whole-Body Counting


  • 4-fluorobenzoyl-polyethylene glycol-cyclo(arginyl-glycyl-aspartyl-tyrosyl-lysyl)
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • Polyethylene Glycols