USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans

Hauger, Olivier; Grenier, N.; Deminère, Colette; Lasseur, Catherine; Delmas, Yahsou; Merville, Pierre; Combe, Christian

doi:10.1007/s00330-007-0660-8

Cited by 64 publications

(51 citation statements)

References 19 publications

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“…Nontargeted SPIO nanoparticles and ultrasmall particles of iron oxide have been used in patients with several types of disease, including renal disease, mostly to detect macrophage accumulation ( 22,23 ). Thus, this is a clinically feasible method with which to detect renal infl ammation.…”

Section: Molecular Imaging: Targeted Iron Oxide Nanoparticles Serkovamentioning

confidence: 99%

Renal Inflammation: Targeted Iron Oxide Nanoparticles for Molecular MR Imaging in Mice

Serkova

Renner²,

Larsen³

et al. 2010

Radiology

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Purpose:To determine the feasibility of T2-weighted magnetic resonance (MR) imaging in the noninvasive quantifi cation of renal infl ammation by using superparamagnetic iron oxide (SPIO) nanoparticles targeted to tissue-bound C3 activation fragments in a mouse model of lupus nephritis. Materials and Methods:All animal procedures were approved by the University of Colorado-Denver animal care and use committee. SPIO nanoparticles were encapsulated by using aminefunctionalized phospholipids. A recombinant protein containing the C3d-binding region of complement receptor type 2 (CR2) was then conjugated to the surface of the SPIO nanoparticle. Five MRL/lpr mice (a model of lupus nephritis) and six C57BL/6 wild-type mice were assessed with T2-weighted MR imaging at baseline and after SPIO injection. The same fi ve MRL/lpr mice and three C57BL/6 mice also underwent MR imaging after injection of CR2-targeted SPIO. A series of T2-weighted pulses with 16 echo times was used to enable precise T2 mapping and calculation of T2 relaxation times in the cortex and outer and inner medulla of the kidneys, as well as in the spleen, muscle, and fat. The effects of treatment and animal genotype on T2 relaxation times were analyzed with repeatedmeasures analysis of variance. Results:At baseline, the T2-weighted signal intensity in the kidneys of MRL/lpr mice was higher than that in the kidneys of wild-type mice. Injection of untargeted SPIO did not alter the T2-weighted signal in the kidneys in either strain of mice. Injection of CR2-targeted SPIO in MRL/lpr mice, however, caused a signifi cant accumulation of targeted iron oxide with a subsequent decrease in T2 relaxation times in the cortex and outer and inner medulla of the kidneys. No changes in T2 relaxation time were observed in the wild-type mice after injection of targeted SPIO. Conclusion:Injection of CR2-conjugated SPIO caused a signifi cant reduction in T2-weighted MR imaging signal and T2 relaxation time in nephritic kidneys.q RSNA, 2010Supplemental material: http://radiology.rsna.org/lookup /suppl

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Section: Molecular Imaging: Targeted Iron Oxide Nanoparticles Serkovamentioning

confidence: 99%

Renal Inflammation: Targeted Iron Oxide Nanoparticles for Molecular MR Imaging in Mice

Serkova

Renner²,

Larsen³

et al. 2010

Radiology

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“…Several USPIOs have been studied in animal models of kidney disease, [2][3][4]6 with at least one having been studied in humans. 8 Ferumoxytol is approved in North America and Europe for the treatment of anemia in chronic renal disease. The clinical availability of this agent and the susceptibility effects induced by this agent on MRI have led to interest in its use in clinical imaging.…”

Section: Discussionmentioning

confidence: 99%

“…19 Hauger and colleagues were amongst the first to publish data in humans on MR imaging in cases of acute or subacute renal failure by measuring changes in the signal intensity that correlated with the amount of infiltrating macrophages. 8 They used a similar USPIO at a lower dose of a maximum of 2.6 mg/kg and proposed use of USPIO-enhanced MR imaging in differentiating inflammatory from non-inflammatory renal disease. To our knowledge, the evolution of quantitative T2* changes in physiologically normal kidneys following intravenous administration of ferumoxytol at high doses (4 and 6 mg/kg) have not been reported previously.…”

mentioning

confidence: 99%

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent

Hedgire¹,

McDermott²,

Wojtkiewicz³

et al. 2014

IJN

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Purpose To evaluate the time-dependent changes in regional quantitative T2* maps of the kidney following intravenous administration of ferumoxytol. Materials and methods Twenty-four individuals with normal kidney function underwent T2*-weighted MRI of the kidney before, immediately after, and 48 hours after intravenous administration of ferumoxytol at a dose of 4 mg/kg (group A, n=12) or 6 mg/kg (group B, n=12). T2* values were statistically analyzed using two-tailed paired t -tests. Results In group A, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.3% and 64.2% for the cortex and 90.8% and 64.6% for the medulla, respectively. In group B, the percentage changes from baseline to immediate post and baseline to 48 hours were 85.2% and 73.4% for the cortex and 94.5% and 74% for the medulla, respectively. This difference was significant for both groups ( P <0.0001). Conclusion There is significant and differential uptake of ferumoxytol in the cortex and medulla of physiologically normal kidneys. This differential uptake may offer the ability to interrogate renal cortex and medulla with possible clinical applications in medical renal disease and transplant organ assessment. We propose an organ of interest based dose titration of ferumoxytol to better differentiate circulating from intracellular ferumoxytol particles.

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“…In these two patients, MRI revealed a clear visible signal loss in all renal compartments, more pronounced in the medulla. Histological examination revealed numerous macrophages, resulting in diagnosis of acute kidney rejection 14 . In experimental autoimmune myocarditis in rats, the iron oxide superparamagnetic and fluorescent nanoparticles provided better image contrast and detectability of focal myocardial inflammation compared to conventional MRI (ref.…”

Section: Vascular Contrast Mediamentioning

confidence: 99%

“…Imaging of inflammation SPIO particles showed not only the ability to image inflammatory processes in vivo 13,14 , but also demonstrated the potential to monitor the effect of anti-inflammatory drugs in a number of studies, both animal 15,16 and human 17 . There are two ways how SPIO particles display the inflammation.…”

Section: Vascular Contrast Mediamentioning

confidence: 99%

Superparamagnetic iron oxide-enhanced magnetic resonance for imaging cardiac inflammation. A minireview

et al. 2015

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USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans

Cited by 64 publications

References 19 publications

Renal Inflammation: Targeted Iron Oxide Nanoparticles for Molecular MR Imaging in Mice

Renal Inflammation: Targeted Iron Oxide Nanoparticles for Molecular MR Imaging in Mice

Evaluation of renal quantitative T2* changes on MRI following administration of ferumoxytol as a T2* contrast agent

Superparamagnetic iron oxide-enhanced magnetic resonance for imaging cardiac inflammation. A minireview

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