Introducing Specificity to Iron Oxide Nanoparticle Imaging by Combining ⁵⁷Fe-Based MRI and Mass Spectrometry

Abstract

Iron oxide nanoparticles (ION) are highly sensitive probes for magnetic resonance imaging (MRI) that have previously been used for in vivo cell tracking and have enabled implementation of several diagnostic tools to detect and monitor disease. However, the in vivo MRI signal of ION can overlap with the signal from endogenous iron, resulting in a lack of detection specificity. Therefore, the long-term fate of administered ION remains largely unknown, and possible tissue deposition of iron cannot be assessed with established methods. Herein, we combine nonradioactive 57Fe-ION MRI with ex vivo laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) imaging, enabling unambiguous differentiation between endogenous iron (56Fe) and iron originating from applied ION in mice. We establish 57Fe-ION as an in vivo MRI sensor for cell tracking in a mouse model of subcutaneous inflammation and for assessing the long-term fate of 57Fe-ION. Our approach resolves the lack of detection specificity in ION imaging by unambiguously recording a 57Fe signature.

Resolving immune cells with patrolling behaviour by magnetic resonance time-lapse single cell tracking

“…However, current labelling approaches have not yet achieved sufficiently high iron concentrations in T cells for time-lapse MRI limiting its applications. Further, restrictions of ION-based MRI regarding signal specificity might be bypassed by using non-radioactive iron isotopes with low natural background [ 31 ]. A contribution of free ION to signal hypointensities detected by time-lapse MRI, appears highly unlikely.…”

“…Free ION were recently shown to be cleared from the blood 24h after i.v. injection, the time when time-laose MRI was performed here [ 31 ]. Further, the small particle size of the administered ION, and the expected velocity of particles flowing with the blood stream renders detection of individual particles with the time-lapse MRI protocol virtually impossible.…”

Magnetic iron oxide nanomaterials: A key player in cancer nanomedicine

“…Masthoff et al combined MRI with ex vivo laser ablation inductively coupled plasma‐mass spectrometry imaging by using nonradioactive 57 Fe‐labeled MIONs as the detection probes. This method could differentiate the administered iron oxides from endogenous iron ( 56 Fe) unambiguously 60 …”

Hepcidin-mediated Iron Regulation in P19 Cells is Detectable by Magnetic Resonance Imaging

“…Cellular iron distribution following extracellular iron supplementation has been studied in conjunction with MRI using non-radioactive iron isotopes to distinguish between pre-existing iron and extracellular supplement 31 . Masthoff and colleagues used both ICP-MS of homogenized tissue and laser ablation ICP-MS (LA-ICP-MS) of tissue slices to quantify endogenous iron ( 56 Fe) and differentiate it from 57 Fe incorporated through uptake of an iron oxide nanoparticle.…”