Synthesis of 68 Ga-Labeled Biopolymer-based Nanoparticle Imaging Agents for Positron-emission Tomography

Anticancer Res. 2019 May;39(5):2415-2427. doi: 10.21873/anticanres.13359.


Aim: The purpose of this study was to develop a folate receptor-targeted 68Ga-labeled agent for the detection of cancer cells in mouse models of ovarian cancer by dual positron-emission tomography (PET) and magnetic resonance imaging (MRI). Moreover, we aimed to develop a controlled biopolymer-based chemistry that enables linking metal-binding (here Ga-68) chelators.

Materials and methods: The nanoparticle (NP) agent was created by self-assembling of folic acid-modified polyglutamic acid and chelator-modified chitosan followed by radiolabeling with 68Ga (III) ions (68Ga-NODAGA-FA). The structure of modified biopolymers was characterized by spectroscopy. Particle size and mobility were determined.

Results: Significant selective binding of NPs was established in vitro using folate receptor-positive KB and - negative MDA-MB-231 cell lines. In vivo tumor uptake of folate-targeted 68Ga3+-radiolabeled NPs was tested using subcutaneous tumor-bearing CB17 SCID mice models. PET/MR dual modalities showed high tumor uptake with 6.5 tumor-to-muscle ratio and NP localization.

Conclusion: In vivo results supporting the preliminary in vitro tests demonstrated considerably higher 68Ga-NODAGA-FA nanoparticle accumulation in KB tumors than in MDA-MB-231 tumors, thereby confirming the folate receptor-mediated uptake of this novel potential PET imaging agent.

Keywords: 68Ga-NODAGA; Poly-gamma-glutamic acid; chitosan; self-assembling nanoparticles; xenograft model.

MeSH terms

  • Acetates / chemistry
  • Animals
  • Chelating Agents / chemistry
  • Chitosan / chemical synthesis
  • Chitosan / chemistry
  • Chitosan / therapeutic use
  • Disease Models, Animal
  • Female
  • Folate Receptor 1 / chemistry
  • Folate Receptor 1 / isolation & purification*
  • Folic Acid / chemistry
  • Gallium Radioisotopes / chemistry*
  • Gallium Radioisotopes / therapeutic use
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Magnetic Resonance Imaging / methods
  • Mice
  • Nanoparticles / chemistry*
  • Nanoparticles / therapeutic use
  • Ovarian Neoplasms / diagnostic imaging*
  • Ovarian Neoplasms / pathology
  • Polyglutamic Acid / chemistry
  • Positron-Emission Tomography / methods


  • 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane
  • Acetates
  • Chelating Agents
  • Folate Receptor 1
  • Folr1 protein, mouse
  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Polyglutamic Acid
  • Chitosan
  • Folic Acid
  • Gallium-68