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

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

Author information

1
BBS Nanotechnology, Debrecen, Hungary.
2
Department of Medical Imaging, Division of Nuclear Medicine and Translational Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
3
Scanomed Ltd, Debrecen, Hungary.
4
University of Debrecen, Doctoral School of Clinical Medicine, Debrecen, Hungary jborbely@med.unideb.hu.
5
BBS Dominus LLC, Debrecen, Hungary.

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.

KEYWORDS:

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

PMID:
31092434
DOI:
10.21873/anticanres.13359
[Indexed for MEDLINE]

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