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

Research output: Contribution to journalArticle

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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Biopolymers
Positron-Emission Tomography
Nanoparticles
Folic Acid
Neoplasms
Chelating Agents
Polyglutamic Acid
SCID Mice
Chitosan
Particle Size
Ovarian Neoplasms
Spectrum Analysis
Metals
Magnetic Resonance Imaging
Ions
Cell Line
Muscles

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Synthesis of 68Ga-labeled biopolymer-based nanoparticle imaging agents for positron-emission tomography. / Körhegyi, Zoltán; Rózsa, Dávid; Hajdu, István; Bodnár, Magdolna; Kertész, István; Kerekes, Krisztina; Kun, Sándor; Kollár, J.; Varga, J.; Garai, Ildikó; Trencsényi, György; Borbély, J.

In: Anticancer research, Vol. 39, No. 5, 01.05.2019, p. 2415-2427.

Research output: Contribution to journalArticle

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, vol. 39, no. 5, pp. 2415-2427. https://doi.org/10.21873/anticanres.13359
Körhegyi, Zoltán ; Rózsa, Dávid ; Hajdu, István ; Bodnár, Magdolna ; Kertész, István ; Kerekes, Krisztina ; Kun, Sándor ; Kollár, J. ; Varga, J. ; Garai, Ildikó ; Trencsényi, György ; Borbély, J. / Synthesis of 68Ga-labeled biopolymer-based nanoparticle imaging agents for positron-emission tomography. In: Anticancer research. 2019 ; Vol. 39, No. 5. pp. 2415-2427.
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AU - Rózsa, Dávid

AU - Hajdu, István

AU - Bodnár, Magdolna

AU - Kertész, István

AU - Kerekes, Krisztina

AU - Kun, Sándor

AU - Kollár, J.

AU - Varga, J.

AU - Garai, Ildikó

AU - Trencsényi, György

AU - Borbély, J.

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N2 - 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.

AB - 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.

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