A Simple and Widely Applicable Method to ⁵⁹Fe-Radiolabel Monodisperse Superparamagnetic Iron Oxide Nanoparticles for In Vivo Quantification Studies

Abstract

A simple, fast, efficient, and widely applicable method to radiolabel the cores of monodisperse superparamagnetic iron oxide nanoparticles (SPIOs) with (59)Fe was developed. These cores can be used as precursors for a variety of functionalized nanodevices. A quality control using filtration techniques, size-exclusion chromatography, chemical degradation methods, transmission electron microscopy, and magnetic resonance imaging showed that the nanoparticles were stably labeled with (59)Fe. Furthermore, the particle structure and the magnetic properties of the SPIOs were unchanged. In a second approach, monodisperse SPIOs stabilized with (14)C-oleic acid were synthesized, and the stability of this shell labeling was studied. In proof of principle experiments, the (59)Fe-SPIOs coated with different shells to make them water-soluble were used to evaluate and compare in vivo pharmacokinetic parameters such as blood half-life. It could also be shown that our radiolabeled SPIOs embedded in recombinant lipoproteins can be used to quantify physiological processes in closer detail than hitherto possible. In vitro and in vivo experiments showed that the (59)Fe label is stable enough to be applied in vivo, whereas the (14)C label is rapidly removed from the iron core and is not adequate for in vivo studies. To obtain meaningful results in in vivo experiments, only (59)Fe-labeled SPIOs should be used.

Intraperitoneal Injection Improves the Uptake of Nanoparticle-Labeled High-Density Lipoprotein to Atherosclerotic Plaques Compared With Intravenous Injection

“…The higher uptake of intravenously injected NP-HDL into the liver led to a more rapid degradation of NP-HDL in the liver. It has been shown by previous studies 19 that when radioactive-labeled SPIOs prepared in the same way as the present study were embedded into triglyceride-rich lipoproteins, lipoproteins underwent faster degradation in the liver. We assume that the radioactivity we observed in the blood 40 minutes after intravenous application was because of free circulating iron.…”

“…For embedding, 10 mg of the lipid extract was dissolved in chloroform and mixed with 0.4 mg iron oxide nanoparticles, or with 5 nmol CdSe/CdS/ZnS core-shell-shell nanoparticles, or with 59 Fe oxide nanoparticles (200 KBq/10 mg lipid). 19 The solvent was removed and the NP-HDLs were resuspended in 4 mL PBS at 65°C, and 0.5 mg deoxycholic acid was added. NP-HDLs were formed by sonication 3 times for 4 minutes in 4 mL PBS.…”

Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy

“…However, newer studies show that internalized SPIO can influence the cell expression pattern (e. g. by oxidative stress), cell proliferation, and cell differentiation [55]. Methods for core labeling (e. g. 59 Fe [56]) and coating labeling with radioisotopes [57] (e. g. 111 In [61]. Headache or back pain, vasodilation, hypotension, or allergic reaction in the form of urticaria can occur on rare occasions [62].…”

Nanomaterials

“…143 Noninvasive MRI has been used to quantify the dose of quantum dot and superparamagnetic iron oxide NM in lipoproteins (micelles) delivered to live animals (mice), 144 however, there are reports detailing the limitation of in vivo quantification of iron as most tissue contains iron and will therefore give a variable background signal. 129 To overcome this issue, Freund et al have developed a new preparation method for the radiolabeling ( 59 Fe) of superparamagnetic iron oxide NM, with 59 Fe monitored inside mice using a large volume Hamburg whole body radioactivity counter. 129 Radiolabeling has subppb (1e5 pg) detection, but thick tissue autoradiography is limited to a spatial resolution of approximately 1 mm.…”

“…127 Atomic spectroscopy has been used in the bulk measurement of Cd levels in the kidneys and liver of mice exposed to Cd-containing quantum dots, 128 but there can be difficulties when attempting to quantify NM dose above that of background elements, for example, the detection of superparamagnetic iron oxide NM above iron levels already present in tissue. 129 …”