Liver positive enhancement after injection of superparamagnetic nanoparticles: Respective role of circulating and uptaken particles

Oswald, Pierre; Clémеnt, Olivier; Chambon, C.; Schouman-Claeys, É.; Frija, G.

doi:10.1016/s0730-725x(97)00004-0

Cited by 96 publications

(70 citation statements)

References 19 publications

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“…23 Another important issue is whether the capacity T-USPIO to target plaque phagocytotic activity in mice will be fully reflective of its targeting efficacy in a human context. Our data in a humanized model of atherosclerosis (ie, LDLr −/− mice with macrophage-specific overexpression of the human macrophage SR-A) 24,29,30 clearly confirm the imaging potential of PP1-equipped USPIO for human inflammatory plaques. From histological plaque analysis, we can exclude differences in lesion size or plaque characteristics between the different groups, confirming that the increased image contrast is attributable to increased T-USPIO ingestion by SR-AI-expressing plaque macrophages.…”

Section: Discussionsupporting

confidence: 70%

Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

Segers

Adel

Bot

et al. 2013

ATVB

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Objective-In search of molecular imaging modalities for specific detection of inflammatory atherosclerotic plaques, we explored the potential of targeting scavenger receptor-AI (SR-AI), which is highly expressed by lesional macrophages and linked to effective internalization machinery. Approach and Results-Ultrasmall superparamagnetic iron oxide particles were conjugated to a peptidic SR-AI ligand (0.371 mol Fe/L and 0.018 mol PP1/L). In vitro incubation of human or murine macrophages with SR-AI-targeted USPIO led to significantly higher iron uptake in vitro than with nontargeted USPIO, as judged by quantitative atomic absorption spectroscopy and Perl's staining. Incremental uptake was strictly mediated by SRs. SR-AI-targeted USPIO displayed accelerated plasma decay and a 3.5-fold increase (P=0.01) in atherosclerotic plaque accumulation on intravenous injection into apolipoprotein E-deficient mice compared with nontargeted USPIO. In addition, atherosclerotic humanized LDLr −/− chimeras with leukocyte expression of human SR-AI showed a significant improvement in contrast-to-noise ratio (2.7-fold; P=0.003) in the atherosclerotic aortic arch plaques 24 hours after injection of SR-AI-targeted USPIO compared with chimeras with leukocyte SR-AI deficiency. Conclusions-Collectively, our data provide several lines of evidence that SR-AI-targeted molecular imaging of USPIO-based contrast agents holds great promise for in situ detection of inflammatory plaques in manifest atherosclerosis. Segers et al SR-AI-Targeted Molecular Imaging of Atherosclerosis 1813screening that displayed high affinity and specificity for SR-AI in vitro in murine and human macrophages. In vivo, PP1 has been shown to accumulate in macrophage-rich organs where it colocalized with F4/80+ macrophages and in atherosclerotic plaques. Furthermore, intravenous injected PP1-coupled fluorescent nanocrystals were successfully accumulated in advanced atherosclerotic plaques of apolipoprotein E-deficient (apoE −/− ) mice. 19In the current study, we report development and validation of SR-AI-targeted USPIO (T-USPIO) functionalized with the aforementioned SR-AI-specific peptide. The T-USPIO was validated in vitro on different mouse and human cell types found in atherosclerotic lesions and also in vivo in an established mouse model for atherosclerosis, as well as in a humanized model of atherosclerosis. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results Relaxivity AnalysisThe contrast agent relaxivities were measured at 37°C at 20, 60, and 400 MHz, respectively (Table). The transverse relaxivities of the SR-A1 and control particle did not differ significantly nor did the longitudinal relaxivity. Increased Scavenger Receptor-AI-Mediated Uptake of T-USPIO In VitroThe kinetics of basal uptake, processing, and detection of USPIO in vitro and in vivo by macrophages have been the subject of numerous studies. 9 Here, we sought to investigate whether USPIO uptake by (plaque associated) macrophages could be augmented by conju...

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Section: Discussionsupporting

confidence: 70%

Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

Segers

Adel

Bot

et al. 2013

ATVB

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“…11 At low concentrations, extracellular iron oxides exert a marked T1 effect in T1-weighted sequences at various field strength (0.5 to 3T), caused by interactions with surrounding protons. [21][22][23][24] The r1 of the nanoparticles decreases with increasing field strength but is higher at 7T than r1 values for gadolinium chelates. 25 The T1 enhancement after Gd-DTPA leakage in the cerebral tissue post-pMCAO showed that the GRE sequence was sensitive to T1-effects of gadolinium at 7T.…”

Section: Discussionmentioning

confidence: 99%

MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia

Wiart

Davoust

Pialat

et al. 2007

Stroke

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Background and Purpose-A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice. Methods-Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours.

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“…The size of intracellular SPIO particles depends on individual Kupffer cell phagocytic activity, because impaired Kupffer cell function could not phagocytize larger particles, only smaller particles (7,17,18).…”

Section: Discussionmentioning

confidence: 99%

Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide‐enhanced magnetic resonance imaging

Tomita

Tanimoto

Irie

et al. 2008

Magnetic Resonance Imaging

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Purpose:To evaluate the utility of noninvasive assessment of human nonalcoholic fatty liver disease (NAFLD) patients using superparamagnetic iron oxide (SPIO)-enhanced MRI. Materials and Methods:Nineteen NAFLD patients underwent SPIO-enhanced MRI. The values of , a time constant for an exponential approximation, were calculated using gradient-echo echo-planar imaging, and the values of %T2, a marker of the T2 relaxation effect of SPIO, were calculated using T2-weighted fast spin-echo images. Correlations between these values and the histological NAFLD activity scores were evaluated. The study protocol was approved by our Institutional Review Board and all patients gave informed consent.Results: There was a statistically significant relationship between the NAFLD activity scores and the values (r ϭ 0.66, P ϭ 0.002). The %T2 values were also significantly correlated with the NAFLD activity score (r ϭ Ϫ0.58, P ϭ 0.009). A cutoff value of 42.8 predicted "definitive NASH" (NAFLD activity score Ն5) with a specificity of 66.7% and a sensitivity of 99.9%, whereas a cutoff %T2 value of 32.5 predicted "definitive NASH" with a specificity of 72.7% and a sensitivity of 87.5%. Conclusion:Noninvasive SPIO-enhanced MRI may be helpful for identifying NASH patients among patients suspected of having NAFLD.

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Liver positive enhancement after injection of superparamagnetic nanoparticles: Respective role of circulating and uptaken particles

Cited by 96 publications

References 19 publications

Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

MRI Monitoring of Neuroinflammation in Mouse Focal Ischemia

Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide‐enhanced magnetic resonance imaging

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