68Ga- and 111In-labelled DOTA-RGD peptides for imaging of alphavbeta3 integrin expression

Eur J Nucl Med Mol Imaging. 2008 Aug;35(8):1507-15. doi: 10.1007/s00259-008-0757-6. Epub 2008 Mar 28.


Purpose: alphavbeta3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [(18)F]Galacto-RGD that monitoring of alphavbeta3 expression is feasible. Here, we introduce (68)Ga- and (111)In-labelled derivatives and compare them with [(18)F]Galacto-RGD.

Methods: For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, alphavbeta3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (alphavbeta3 positive) and M21-L (alphavbeta3 negative) cells were used.

Results: Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [(68)Ga]DOTA-RGD and only up to 1.4% for [(111)In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in alphavbeta3-positive tumours was 2.9 +/- 0.3%ID/g and in alphavbeta3-negative tumours 0.8 +/- 0.1%ID/g for [(68)Ga]DOTA-RGD ([(111)In]DOTA-RGD: 1.9 +/- 0.3%ID/g and 0.5 +/- 0.2%ID/g; [(18)F]Galacto-RGD: 1.6 +/- 0.2%ID/g and 0.4 +/- 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [(68)Ga]DOTA-RGD, tumour/blood ratios were higher for [(111)In]DOTA-RGD and [(18)F]Galacto-RGD. However, microPET studies demonstrated that visualisation of alphavbeta3-positive tumours using [(68)Ga]DOTA-RGD is possible.

Conclusions: Our data indicate that [(68)Ga]DOTA-RGD allows monitoring of alphavbeta3 expression. Especially, the much easier radiosynthesis compared to [(18)F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [(18)F]Galacto-RGD remains superior for imaging alphavbeta3 expression. Introduction of alternative chelator systems may overcome the disadvantages.

MeSH terms

  • Animals
  • Gene Expression Profiling / methods*
  • Integrin alphaVbeta3 / metabolism*
  • Melanoma / blood supply
  • Melanoma / diagnostic imaging
  • Melanoma / metabolism
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Probe Techniques
  • Neovascularization, Pathologic / diagnostic imaging*
  • Neovascularization, Pathologic / metabolism*
  • Organ Specificity
  • Organometallic Compounds / pharmacokinetics*
  • Peptides, Cyclic / pharmacokinetics*
  • Radionuclide Imaging
  • Tissue Distribution


  • 111In-DOTA-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
  • 68Ga-DOTA-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
  • Integrin alphaVbeta3
  • Organometallic Compounds
  • Peptides, Cyclic