Synthesis and biological evaluation of a (99m)Tc-labelled cyclic RGD peptide for imaging the alphavbeta3 expression

Nuklearmedizin. 2004 Feb;43(1):26-32. doi: 10.1267/nukl04010026.


Aim: The alphavbeta3 integrin is involved in tumour induced angiogenesis and tumour metastasis. We describe the synthesis and evaluation of a (99m)Tc-labelled RGD analogue for the visualisation of alphavbeta3 integrin expression.

Methods: The linear peptides were assembled on a solid support. Cyclisation was performed under high dilution conditions. For conjugation with the chelator peptide, a water soluble carbodiimide was used. Radiolabelling was carried out due to standard procedures with high radiochemical yield and radiochemical purity. For in vivo evaluation, nude mice bearing alphavbeta3-positive human melanoma M21 and alphav-negative human melanoma M21-L or Balb/c mice bearing alphav-positive murine osteosarcoma were used.

Results: Activity accumulation of (99m)Tc-DKCK-RGD 240 min p. i. was 1.1% ID/g in the alphavbeta3-positive melanoma and 0.3% ID/g in the negative control tumour. In the osteosarcoma model 2.2% ID/g was found 240 min p. i. Planar gamma camera images allowed contrasting visualisation of alphavbeta3-positive tumours 240 min p. i. Blocking of the tumour using the alphavbeta3-selective pentapeptide cyclo(-Arg-Gly-Asp-D-Phe-Val-) reduces activity accumulation in the tumour to background level. However, 240 min p. i. highest activity concentration was found in kidneys resulting in low tumour/kidney ratios. Metabolite analysis 240 min p. i. showed approximately 60% intact tracer in kidneys and 80% in the tumour. Only 24% intact tracer was found in blood 30 min p. i.

Conclusion: (99m)Tc-DKCK-RGD allows imaging of alphavbeta3-positive tumours in mice. However, pharmacokinetics as well as metabolic stability of the tracer have to be improved for potential clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biotransformation
  • Bone Neoplasms / diagnostic imaging*
  • Integrin alphaVbeta3 / analysis*
  • Mice
  • Mice, Inbred BALB C
  • Oligopeptides / chemical synthesis
  • Oligopeptides / pharmacokinetics*
  • Osteosarcoma / diagnostic imaging*
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / pharmacokinetics
  • Radionuclide Imaging
  • Technetium / pharmacokinetics*
  • Tissue Distribution


  • Integrin alphaVbeta3
  • Oligopeptides
  • Peptides, Cyclic
  • Technetium
  • arginyl-glycyl-aspartic acid