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

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.

Preliminary Evaluation of Iron Oxide Nanoparticles Radiolabeled with 68Ga and 177Lu as Potential Theranostic Agents

“…Similar nanosystems reported by Papadopoulou et al, with a highly negative surface charge (−36 mV versus−40 mV in the case of [ 68 Ga]Ga-MA), seem to have more interactions with macrophages and highly accumulate in organs such as the liver and spleen but also in lungs, especially at 30 min p.i. [ 45 ]. In most cases reported, surface functionalization with a biocompatible coating displays similar in vivo biodistribution as in the case of [ 68 Ga]Ga-MAPEG.…”

“…Previous studies mention the development of iron oxide nanoparticles with a condensed magnetic core, decorated with different polymers and, in some cases, with targeting moieties [ 42 , 43 , 44 , 45 , 46 ]. The condensed clustering structure refers to the in situ clustering of MIONs during crystal growth, in such a fashion that the individual MIONs adopt the same crystallographic orientation with their neighboring crystals through epitaxial aggregation [ 42 , 47 , 48 ].…”

Synthesis and In Vitro Evaluation of Gold Nanoparticles Functionalized with Thiol Ligands for Robust Radiolabeling with 99mTc

“…The metabolic activity of the cells is proportional to the color density of the purple formazan crystals. For these reasons, MTT assay can be used as an indicator for cell viability and cytotoxicity [ 31 , 32 ].…”

Radiolabeling of Nanomaterials: Advantages and Challenges

“…In the existing literature, the radiochemical stability of the NMs-radiometals complex has always been investigated ex vivo as follows: after the direct (chelator-free) or indirect (typically chelator-based) chemical bond formation between the radiometals and the NMs surface, the complex is incubated in simulated body fluids (i.e., serum or PBS at 37°C) for several hours or overnight, and then the detached radiometals are collected and quantified by means of centrifugation, chromatography, or liquid chromatography ( Korany et al, 2020 ; Wang L. Z. et al, 2020 ; Papadopoulou et al, 2021 ). However, one of our work just demonstrated that some features of the particokinetics may lead to a previously underappreciated loss in the in vivo stability of radiolabeling ( Zhang et al, 2019 ).…”