Synthesis of 68Ga-labeled biopolymer-based nanoparticle imaging agents for positron-emission tomography

Zoltán Körhegyi, Dávid Rózsa, István Hajdu, Magdolna Bodnár, István Kertész, Krisztina Kerekes, Sándor Kun, J. Kollár, J. Varga, Ildikó Garai, György Trencsényi, J. Borbély

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2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2415-2427
Number of pages13
JournalAnticancer research
Volume39
Issue number5
DOIs
Publication statusPublished - May 1 2019

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Keywords

  • Ga-NODAGA
  • Chitosan
  • Poly-gamma-glutamic acid
  • Self-assembling nanoparticles
  • Xenograft model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Körhegyi, Z., Rózsa, D., Hajdu, I., Bodnár, M., Kertész, I., Kerekes, K., Kun, S., Kollár, J., Varga, J., Garai, I., Trencsényi, G., & Borbély, J. (2019). Synthesis of 68Ga-labeled biopolymer-based nanoparticle imaging agents for positron-emission tomography. Anticancer research, 39(5), 2415-2427. https://doi.org/10.21873/anticanres.13359