Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

Alam, Shirjel; Tse, George; Stirrat, Colin; MacGillivray, Tom; Lennen, Ross J.; Jansen, Maurits A.; Newby, David E.; Marson, Lorna; Henriksen, Peter

doi:10.1155/2015/507909

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…USPIO-enhanced T2* MRI has previously been used in man to assess cardiovascular inflammation in a range of different conditions,5–8 11 and preclinical models suggest this technique may be useful in assessing human patients with transplant rejection 4 13–17. In our cohort of stable patients with cardiac transplantation, we did not detect greater USPIO enhancement within the myocardium, but this contrasted with the increased measures of myocardial T2 found in transplant patients compared with volunteers.…”

Section: Discussioncontrasting

confidence: 57%

“…Promising preclinical studies have shown USPIO-enhanced MRI is able to detect acute cardiac and renal allograft rejection with USPIO signal correlating with macrophage distribution, rejection severity on histology and impaired cardiac function. Moreover, this approach can also be used to assess treatment response with rodent models demonstrating less USPIO enhancement following initiation of immunosuppression 4 13–17. A future role of USPIOs includes a ‘theranostic’ strategy whereby imaging is combined with therapy; Guo et al 18 recently conjugated an iron nanoparticle to a CD-3 antibody and a therapy gene, allowing imaging and targeting of T cells that play a central role in acute cardiac allograft rejection.…”

Section: Introductionmentioning

confidence: 99%

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Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation

et al. 2019

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ObjectivesUltra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac transplant rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with transplant rejection.MethodsTen volunteers and 11 patients with cardiac transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months.ResultsTen patients with clinically stable cardiac transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43).ConclusionStable patients with cardiac transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac transplant rejection.Trial registration numberNCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24.

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Section: Discussioncontrasting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation

et al. 2019

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“…Thus, targeting of macrophages (usually total population or M1 fraction) has been pursued in preclinical imaging of several diseases by MRI, either by passive labeling or by active targeting of membrane receptors with vectorized nanoprobes 18 - 21 . Tracking of macrophage infiltration by MRI has been employed in models of kidney transplantation, fibrosis and ischemia-reperfusion 22 - 26 . Recent studies have been designed to detect M1/M2 macrophage polarization by MRI in animal models 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles

Rubio‐Navarro¹,

Carril²,

Padró³

et al. 2016

Theranostics

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Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.

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MRI for diagnosis of post-renal transplant complications: current state-of-the-art and future perspectives

Schutter

Lantinga

Borra

et al. 2019

Magn Reson Mater Phy

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Kidney transplantation has developed into a widespread procedure to treat end stage renal failure, with transplantation results improving over the years. Postoperative complications have decreased over the past decades, but are still an important cause of morbidity and mortality. Early accurate diagnosis and treatment is the key to prevent renal allograft impairment or even graft loss. Ideally, a diagnostic tool should be able to detect post-transplant renal dysfunction, differentiate between the different causes and monitor renal function during and after therapeutic interventions. Non-invasive imaging modalities for diagnostic purposes show promising results. Magnetic resonance imaging (MRI) techniques have a number of advantages, such as the lack of ionizing radiation and the possibility to obtain relevant tissue information without contrast, reducing the risk of contrast-induced nephrotoxicity. However, most techniques still lack the specificity to distinguish different types of parenchymal diseases. Despite some promising outcomes, MRI is still barely used in the post-transplantation diagnostic process. The aim of this review is to survey the current literature on the relevance and clinical applicability of diagnostic MRI modalities for the detection of various types of complications after kidney transplantation.

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Nanoparticle Enhanced MRI Scanning to Detect Cellular Inflammation in Experimental Chronic Renal Allograft Rejection

Cited by 3 publications

References 38 publications

Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation

Ferumoxytol-enhanced MRI in patients with prior cardiac transplantation

CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles

MRI for diagnosis of post-renal transplant complications: current state-of-the-art and future perspectives

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