Chelator-Free/Chelator-Mediated Radiolabeling of Colloidally Stabilized Iron Oxide Nanoparticles for Biomedical Imaging.

Sofia Papadopoulou,Argiris Kolokithas-Ntoukas,Maria Paravatou-Petsotas,Stavros Xanthopoulos,Penelope Bouziotis,Charalampos Tsoukalas,Aristides Bakandritsos,Evangelia-Alexandra Salvanou,Maria Gazouli,Konstantinos Avgoustakis,Anastasios Gaitanis

doi:10.3390/nano11071677

Abstract

The aim of this study was to develop a bioimaging probe based on magnetic iron oxide nanoparticles (MIONs) surface functionalized with the copolymer (p(MAA-g-EGMA)), which were radiolabeled with the positron emitter Gallium-68. The synthesis of the hybrid MIONs was realized by hydrolytic condensation of a single ferrous precursor in the presence of the copolymer. The synthesized MagP MIONs displayed an average Dh of 87 nm, suitable for passive targeting of cancerous tissues through the enhanced permeation and retention (EPR) effect after intravenous administration, while their particularly high magnetic content ascribes strong magnetic properties to the colloids. Two different approaches were explored to develop MIONs radiolabeled with 68Ga: the chelator-mediated approach, where the chelating agent NODAGA-NHS was conjugated onto the MIONs (MagP-NODAGA) to form a chelate complex with 68Ga, and the chelator-free approach, where 68Ga was directly incorporated onto the MIONs (MagP). Both groups of NPs showed highly efficient radiolabeling with 68Ga, forming constructs which were stable with time, and in the presence of PBS and human serum. Ex vivo biodistribution studies of [68Ga]Ga- MIONs showed high accumulation in the mononuclear phagocyte system (MPS) organs and satisfactory blood retention with time. In vivo PET imaging with [68Ga]Ga-MagP MIONs was in accordance with the ex vivo biodistribution results. Finally, the MIONs showed low toxicity against 4T1 breast cancer cells. These detailed studies established that [68Ga]Ga- MIONs exhibit potential for application as tracers for early cancer detection.

Highlights

In the pursuit of more effective cancer targeting probes, radiolabeled nanoparticles have attracted intense scientific interest for their great potential in nuclear medicine
The chelating agent NODAGA-NHS was conjugated onto the surface of the magnetic iron oxide nanoparticles (MIONs) (MagP-NODAGA) to form a chelate complex with 68 Ga in the chelator-mediated approach
The synthesis of the hybrid MIONs was realized by hydrolytic condensation of a single ferrous precursor in the presence of the p(MAA-g-EGMA) copolymer acting as the surface functionalizing agent through a simple self-assembly process

Summary

Introduction

In the pursuit of more effective cancer targeting probes, radiolabeled nanoparticles have attracted intense scientific interest for their great potential in nuclear medicine. Nanomaterials 2021, 11, 1677 development of numerous nanoparticle types of different size, shape, and core material as versatile platforms for various applications. Nanoparticles are radiolabeled with beta (β)- or alpha (α)-emitting isotopes such as Lutetium-177 [177 Lu] and Actinium225 [225 Ac], respectively [9,10,11]. The functionalization of these nanoparticles with various moieties transforms them into multimodal theranostic or therapeutic systems [14,15]. Radiolabeled particles that incorporate drugs can be used for image-guided drug delivery or controlled release with synergistic therapeutic effects (e.g., by combining radio- and chemotherapy) [16,17,18]

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