Gallium-68 Labeled Iron Oxide Nanoparticles Coated with 2,3-Dicarboxypropane-1,1-diphosphonic Acid as a Potential PET/MR Imaging Agent: A Proof-of-Concept Study

Abstract

The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity (>91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that 68Ga-Fe3O4-DPD MNPs could serve as an important diagnostic tool for biomedical imaging.

The analysis of 2,3-dicarboxypropane-1,1-diphosphonic acid-coated magnetite nanoparticles under an external magnetic field and their radiolabeling for possible theranostic applications

“…Synthesis and detailed physicochemical properties of Fe 3 O 4 -DPD MNPs were previously described. 7 Briefly, after synthesis of Fe 3 O 4 MNPs by coprecipitation method, DPD water solution (Fe 3 O 4 :DPD=1:1) was added and the coating reaction was carried out overnight at room temperature. The excess of unreacted DPD was removed by dialysis against deionized water for one day.…”

“…6 Radiolabeling of MNPs with gamma or positron emitters allows combined hyperthermia treatment and MRI/PET or MRI/SPECT imaging. 7,8 In contrast, labeling with beta emitters provides an opportunity for MRI diagnostic and dual hyperthermiaradionuclide therapy.…”

“…The 2,3-dicarboxypropane-1,1diphosphonic acid (DPD) is water soluble and biocompatible bisphosphonate which provide suitable dispersion stability and reduces the cytotoxicity of the naked Fe 3 O 4 MNPs. 6,7 In addition, DPD as a tetradentate ligand, serves as an effective chelator. Complex DPD with 99m Tc has been widely accepted for bone scintigraphy because of its high sensitivity and easy evaluation of the whole skeletal system.…”

“…15 Conjugation of DPD to the surface of iron oxide MNPs and their labeling with 68 Ga, make them suitable for PET/MRI imaging. 7 Please do not adjust margins…”

Molecular Imaging with 68Ga Radio-Nanomaterials: Shedding Light on Nanoparticles

“…They also observed significant accumulation in the lungs, suggesting nanoparticle clustering or aggregation. Karageorgou et al [105] obtained a dual PET/MRI nanoradiotracer composed by iron oxide nanoparticles conjugated to DPD, a tetradentate ligand (with two phosphonates and two carboxylate groups) that apart from acting as surfactant, serves as 68 Ga chelator. They obtained a 70% radiolabeling yield and a >91% chemical purity.…”