Association between [68Ga]NODAGA-RGDyK uptake and dynamics of angiogenesis in a human cell-based 3D model

Mol Biol Rep. 2021 Jun;48(6):5347-5353. doi: 10.1007/s11033-021-06513-8. Epub 2021 Jul 2.


Radiolabeled RGD peptides targeting expression of αvβ3 integrin have been applied to in vivo imaging of angiogenesis. However, there is a need for more information on the quantitative relationships between RGD peptide uptake and the dynamics of angiogenesis. In this study, we sought to measure the binding of [68Ga]NODAGA-RGDyK to αvβ3 integrin in a human cell-based three-dimensional (3D) in vitro model of angiogenesis, and to compare the level of binding with the amount of angiogenesis. Experiments were conducted using a human cell-based 3D model of angiogenesis consisting of co-culture of human adipose stem cells (hASCs) and of human umbilical vein endothelial cells (HUVECs). Angiogenesis was induced with four concentrations (25%, 50%, 75%, and 100%) of growth factor cocktail resulting in a gradual increase in the density of the tubule network. Cultures were incubated with [68Ga]NODAGA-RGDyK for 90 min at 37 °C, and binding of radioactivity was measured by gamma counting and digital autoradiography. The results revealed that tracer binding increased gradually with neovasculature density. In comparison with vessels induced with a growth factor concentration of 25%, the uptake of [68Ga]NODAGA-RGDyK was higher at concentrations of 75% and 100%, and correlated with the amount of neovasculature, as determined by visual evaluation of histological staining. Uptake of [68Ga]NODAGA-RGDyK closely reflected the amount of angiogenesis in an in vitro 3D model of angiogenesis. These results support further evaluation of RGD-based approaches for targeted imaging of angiogenesis.

Keywords: Angiogenesis; Positron emission tomography.

MeSH terms

  • Acetates / pharmacokinetics*
  • Acetates / pharmacology
  • Angiogenesis Inducing Agents / pharmacology
  • Cell Culture Techniques, Three Dimensional / methods
  • Cell Line, Tumor
  • Endothelial Cells
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics*
  • Heterocyclic Compounds, 1-Ring / pharmacology
  • Humans
  • Integrin alphaVbeta3 / metabolism
  • Isotope Labeling / methods
  • Models, Biological
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology*
  • Oligopeptides / pharmacokinetics*
  • Oligopeptides / pharmacology
  • Tissue Distribution


  • 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
  • Acetates
  • Angiogenesis Inducing Agents
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Integrin alphaVbeta3
  • Oligopeptides
  • arginine-glycine-aspartate-O-methyltyrosine amide
  • arginyl-glycyl-aspartic acid