Synthesis of acid-stabilized iron oxide nanoparticles and comparison for targeting atherosclerotic plaques: Evaluation by MRI, quantitative MPS, and TEM alternative to ambiguous Prussian blue iron staining

Labeling of mesenchymal stem cells for MRI with single-cell sensitivity

“…All preparations for magnetic particle spectroscopy (MPS) were carried out with a ceramic dissecting set to prevent false results through possible abrasion of magnetic material, as previously described by Scharlach et al 51 Mouse brains were longitudinally cut in two halves (right and left). Each half was fit into 0.1 mL polymerase chain reaction (PCR) tubes for MPS.…”

“…In the past decade, VSOP have been further developed in our laboratory for magnetic resonance angiography and MRI of atherosclerotic plaques. [47][48][49][50][51] They have been tested for MSC labeling and MRI detection with single-cell sensitivity.…”

Uptake of citrate-coated iron oxide nanoparticles into atherosclerotic lesions in mice occurs via accelerated transcytosis through plaque endothelial cells

“…In agreement with these instability-associated targets, the loss of MRI signal caused by VSOPs was reported to correlate with histological plaque instability criteria [18]. Recently, a study comparing VSOP variants stabilized with different monomeric organic acids detected VSOP-filled vesicular structures in the cytoplasm of plaque endothelial cells (ECs) 3 h after VSOP injection [17]. This observation adds an important new aspect to the discussion on potential VSOP uptake mechanisms.…”

“…We recorded T2*-weighted in situ and ex vivo MRI scans of the thoracic aorta at time points ranging from 10 min to 24 h after intravenous injection of VSOPs. VSOPs are rapidly cleared from the blood, mainly by liver and spleen, with a blood half-life of around 30 min [17], indicating that early time points after injection are the most important for uptake analyses. In vivo MR imaging of VSOP accumulation in plaques is difficult within the first two blood halflives, since during that period the high intravascular VSOP concentration has a strong T2* effect that prevents adequate visualization of the vessel wall [22].…”

“…In vitro experiments in THP-1 monocytic cells demonstrated that the rapid cellular VSOP uptake depends on an interaction with cell surface glycosaminoglycans (GAGs) [15]. In vivo MRI studies in apolipoprotein E-deficient (ApoE −/− ) mice revealed an increasing uptake of VSOPs into atherosclerotic lesions over the course of disease progression and identified plaque macrophages as imaging targets [16,17]. Plaque analyses in atherosclerotic rabbits confirmed VSOP accumulation in macrophages and uncovered GAGcontaining microvesicles as additional imaging targets [18].…”