scholarly journals Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

2014 ◽  
pp. 4211 ◽  
Author(s):  
Harald Mangge ◽  
Gunter Almer ◽  
Kelli Summers ◽  
Bernhard Scheicher ◽  
Josef Kellner ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Interleukin 10 ◽  
Atherosclerotic Lesions ◽  
Coated Nanoparticle

scholarly journals Anti-inflammatory mediators for molecular imaging of atherosclerosis

2014 ◽  
Vol 6 (2) ◽  
Author(s):  
Gunter Almer ◽  
Peter Opriessnig ◽  
Ruth Prassl ◽  
Harald Mangge
Keyword(s):  
Myocardial Infarction ◽  
Molecular Imaging ◽  
Inflammatory Mediators ◽  
Vascular Wall ◽  
Interleukin 10 ◽  
Clinical Endpoints ◽  
Atherosclerotic Lesions ◽  
Immune Mediated ◽  
Anti Inflammatory ◽  
Inflammatory Molecules

AbstractNanomedicine, a young and innovative field, offers interesting approaches for diagnosis and treatment in personalized medicine. Myocardial infarction and stroke belong to the most important challenges in this context because an improved early diagnosis of individuals well before fatal clinical endpoints occur is urgently needed. The underlying cause of myocardial infarction and stroke is atherosclerosis, a chronic immune-mediated inflammation of the vascular wall involving monocytes, macrophages, T-lymphocytes, and arterial wall cells. Hence, an immense number of pro-inflammatory mediators have been investigated in the context of nanomedicine and atherosclerosis but, interestingly, only few anti-inflammatory biomarkers. Nevertheless, the anti-inflammatory axis is always present as a negative feedback if a critical inflammatory perpetuation destabilizes atherosclerotic lesions. Hence, we could show that the immune-modulating, anti-inflammatory molecules, adiponectin and interleukin-10, are useful for molecular imaging of AS plaques. Based on recent publications in animal models of atherosclerosis, we strongly assume that the inflammatory “brake” mechanisms may represent an interesting new tool to specifically target the scenario of culprit AS-lesions. In this review article we discuss the potential of adiponectin, interleukin-10 and other anti-inflammatory active molecules like targeted liposomes and high dense lipoproteins towards this.

Abstract 1079: Modulation of Atherosclerotic Plaque Characteristics by Minocycline: An Evaluation by Molecular Imaging of Matrix Metalloprotainase (MMP) Expression

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Satoru Ohshima ◽  
Shinichiro Fujimoto ◽  
Hironori Nakagami ◽  
Nezam Haider ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Molecular Imaging ◽  
Low Dose ◽  
High Cholesterol Diet ◽  
High Dose ◽  
Targeted Interventions ◽  
Mmp Inhibitor ◽  
Atherosclerotic Lesions

MMP activation in atherosclerotic lesions plays an important role in plaque progression and vulnerability, and is a potential target for plaque stabilization. We evaluated the effectiveness of minocycline (MC) in modulation of plaque characteristics using molecular imaging of MMP expression, compared with fluvastatin (FS). 38 NZW rabbits with experimental atherosclerotic lesions were subjected to in vivo micro SPECT/CT imaging for the assessment of MMP activity using 99mTc-labeled broad spectrum MMP inhibitor (MPI). Atherosclerotic lesions were produced by balloon deendotheliazation of abdominal aorta, and high cholesterol diet for 4 months. Of these, 7 received low dose MC (1.5mg/kg), 7 high dose MC (3mg/kg, N=7), 6 FS (1mg/kg), and 6 combination of low dose MC and FS (MC+FS) in the fourth month, 12 received no intervention (Rx-control). 8 unmanipulated normal chow-fed rabbits were used as disease controls (Dz-control). After in vivo imaging, aortas were explanted for %ID/g MPI uptake, histological characterization, and MMP activity assays. Parallel in vitro studies were performed for the effect of MC and FS on NF-κB, VCAM-1 and MMP-9 expression from cultured TNF-α-stimulated smooth muscle cells and macrophages. Target accumulation of MPI was best visualized in atherosclerotic aorta in Rx-control atherosclerotic rabbits. % ID/g MPI in Rx-control (.10±.04%) was significantly higher than Dz-control (.016±.004%), MC-low (.081±.02%) and high (.045±.01%) dose, FS (.056±.011%), and MC+FS (.049±.005%) rabbits, and showed a significant correlation with histologically and biochemically-verified MMP-2, -9 activity. MC-treated plaques showed marked reduction in inflammation and increase in smooth muscle content. In vitro cell culture confirmed that NF-κB and VCAM-1 expression in activated VSMC were reduced by MC, and that MMP-9 expression in activated macrophage was also inhibited by MC. The present study demonstrates that MC is equally effective as FS in modulation of plaque characteristics, and that molecular imaging can characterize various biologic processes in vivo and allows for the study of the efficacy of targeted interventions.

P1217Zirconium-89 labelled probe for molecular imaging of inflammation in experimental atherosclerosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Ahmed ◽  
T Tegnebratt ◽  
T Tran ◽  
P Damberg ◽  
D Bone ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ex Vivo ◽  
Vascular Inflammation ◽  
Imaging Study ◽  
Experimental Atherosclerosis ◽  
Plaque Morphology ◽  
Atherosclerotic Lesions ◽  
18F Fdg ◽  
Gamma Counter

Abstract Background Early detection of inflamed atherosclerotic lesions by molecular imaging might improve risk assessment beyond that of vascular stenosis and plaque morphology imaging, and improve the clinical management of high-risk patients. Purpose To target the key features of unstable atherosclerotic lesions, we studied the feasibility of our radiotracer, based on modified human serum albumin (HSA), to identify inflamed atherosclerotic lesions by in vivo molecular imaging. Methods We applied a maleylated HSA (Mal-HSA) probe, recognised by scavenger receptors on macrophages, in an experimental in vivo imaging study of atherosclerosis. Mal-HSA was coupled with a positron-emittingmetal ion, Zirconium-89 (89Zr). The targeting potential of this probe was evaluated and compared with unspecific 89Zr-HSA and 18F-FDG in a mouse model of atherosclerosis (Apoe−/−, n=22) and compared with wild-type (WT) mice (C57BL/6, n=21) as controls. Radiotracer accumulation in the aortic arch was analysed in vivo by the fusion of positron emission tomography–magnetic resonance imaging (PET-MRI), radiotracer bio-distribution was measured ex vivo by gamma counter, and plaque uptake was evaluated by phosphor imaging (PI) autoradiography (ARG). Results PET-MRI, gamma counter measurements, and PI-ARG showed the accumulation of 89Zr-Mal-HSA in the atherosclerotic lesions of Apoe−/− mice. The maximum standardised uptake value (SUVmax) for 89Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe−/− mice than control WT mice, whereas no difference in SUVmax was found for 18F-FDG in the same animals. 89Zr-Mal-HSA uptake in the aorta as evaluated by gamma counter 48 h post-injection was 32% higher (P<0.01) for Apoe−/− mice compared to WT mice, and the aorta-to-blood ratio was 10-fold higher (P<0.001) for 89Zr-Mal-HSA compared with unspecific 89Zr-HSA. HSA probes were mainly distributed to the liver, spleen, kidneys, bone and lymph nodes. The PI-ARG results corroborated the PET and gamma counter measurements, showing higher accumulation of 89Zr-Mal-HSA in the aortas of Apoe−/− mice compared to WT mice; 9.4±1.4 vs 0.8±0.3% (P<0.001). Conclusions The modified HSA-based radiotracer showed in vivo targeting of inflamed atherosclerotic lesions of mouse aorta, which could also be verified ex vivo. 89Zr-Mal-HSA seems to be a promising diagnostic tool for the identification of vascular inflammation. Further methodological studies are needed to verify its applicability for detecting rupture-prone plaques. Acknowledgement/Funding Swedish Research Council (22036); the Swedish HLF (20150423, 20170669); ALF (20150517, 447561, 726481); Söderberg Foundations, VINNOVA and KI

scholarly journals Label-free molecular imaging of atherosclerotic lesions using multimodal nonlinear optical microscopy

2007 ◽  
Vol 12 (5) ◽  
pp. 054007 ◽  
Author(s):  
Thuc T. Le ◽  
Ingeborg M. Langohr ◽  
Matthew J. Locker ◽  
Michael Sturek ◽  
Ji-Xin Cheng
Keyword(s):  
Molecular Imaging ◽  
Optical Microscopy ◽  
Nonlinear Optical ◽  
Label Free ◽  
Nonlinear Optical Microscopy ◽  
Atherosclerotic Lesions

Abstract 1454: Targeted Molecular Imaging Probes For In Vivo MR Detection Of Atherosclerotic Lesions Using Antibodies Against Oxidized Low Density Lipoprotein

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Karen C Briley-Saebo ◽  
Willem Mulder ◽  
Peter X Shaw ◽  
Seung-Hyuk Choi ◽  
Venkatesh Mani ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Mr Imaging ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atherosclerotic Lesions ◽  
Molecular Imaging Probes ◽  
Imaging Probes

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the initiation, progression and destabilization of atherosclerotic plaque. Molecular imaging probes that target OxLDL may allow in vivo detection of vulnerable plaques. In this study, magnetic resonance imaging (MRI) was used to detect atherosclerotic lesions in apolipoprotein deficient mice (ApoE−/−) using micelles comprised of gadolinium lipids, fluorescent rhodamine, PEG-lipids, and MDA2, a murine monoclonal antibody that binds malondialdehyde (MDA) lysine epitopes present in OxLDL. Materials and Results: Untargeted micelles, MDA2-labeled micelles and nonspecific polyclonal IgG micelles were prepared and characterized with respect to OxLDL binding capacity, pharmacokinetics, and biodistribution in wild type (WT) and ApoE−/− mice. MR imaging was performed at 9.4T over a 3-week interval after administration of 0.075 mmol Gd/kg micelles. MDA2 increased the micelle size, blood half-life, and MR efficacy relative to untargeted and IgG-micelles. Maximal plaque enhancement (>125%) was observed 72 hours post MDA2-micelle injection (Figure ). Untargeted and IgG-micelles did not exhibit significant wall enhancement at any of the time points studied. Confocal microscopy revealed that MDA2-micelles accumulate within foam cells associated with atherosclerotic plaque. WT mice showed no significant MR wall enhancement for any of the micelles studied. Conclusions: MR imaging using MDA2-micelles demonstrates specific targeting of OxLDL and foam cells and provides excellent MR image quality. This study suggests that it may be feasible to image similar atherosclerotic lesions in humans with MRI.

scholarly journals In Vivo Molecular Imaging of Atherosclerotic Lesions in ApoE-/- Mice Using VCAM-1-Specific, 99mTc-Labeled Peptidic Sequences

2013 ◽  
Vol 54 (8) ◽  
pp. 1442-1449 ◽  
Author(s):  
J. Dimastromatteo ◽  
A. Broisat ◽  
P. Perret ◽  
M. Ahmadi ◽  
D. Boturyn ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Atherosclerotic Lesions

scholarly journals Molecular Imaging of Matrix Metalloproteinase in Atherosclerotic Lesions

2008 ◽  
Vol 52 (23) ◽  
pp. 1847-1857 ◽  
Author(s):  
Shinichiro Fujimoto ◽  
Dagmar Hartung ◽  
Satoru Ohshima ◽  
D. Scott Edwards ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Matrix Metalloproteinase ◽  
Atherosclerotic Lesions

scholarly journals Interleukin-10: An Anti-Inflammatory Marker To Target Atherosclerotic Lesions via PEGylated Liposomes

2012 ◽  
Vol 10 (1) ◽  
pp. 175-186 ◽  
Author(s):  
Gunter Almer ◽  
Daniela Frascione ◽  
Isabella Pali-Schöll ◽  
Caroline Vonach ◽  
Anna Lukschal ◽  
...  
Keyword(s):  
Inflammatory Marker ◽  
Interleukin 10 ◽  
Pegylated Liposomes ◽  
Atherosclerotic Lesions ◽  
Anti Inflammatory

scholarly journals Targeting Elastase for Molecular Imaging of Early Atherosclerotic Lesions

2017 ◽  
Vol 37 (3) ◽  
pp. 525-533 ◽  
Author(s):  
Almut Glinzer ◽  
Xiaopeng Ma ◽  
Jaya Prakash ◽  
Melanie A. Kimm ◽  
Fabian Lohöfer ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Atherosclerotic Lesions

Abstract 5790: Dual Molecular Imaging for Assessment of Matrix Metalloproteinase and Apoptosis in Atherosclerotic Lesions before and after Statin Therapy

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shinichiro Fujimoto ◽  
Dagmar Hartung ◽  
D. Scott Edwards ◽  
Michael Azure ◽  
Jun Zhou ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Matrix Metalloproteinase ◽  
Statin Therapy ◽  
Ex Vivo ◽  
Tracer Uptake ◽  
Lipid Lowering ◽  
Atherosclerotic Lesions ◽  
Normal Chow ◽  
The Impact

We evaluated the correlation between matrix metalloproteinase (MMP) and apoptotic activities in atherosclerosis lesions, and the impact of lipid lowering by dietary modification and statin therapy employing molecular imaging with Tc-99m broad MMP inhibitor (MPI) and indium-111 annexin A5 (AA5). Atherosclerosis was produced in 13 New Zealand White rabbits by balloon deendothelialization and hypercholesterolemic diet for 4 months; 6 unmanipulated rabbits on normal chow were used as controls. In the last month, 3 of the 13 atherosclerotic rabbits were changed to normal chow, and 4 received fluvastatin (1mg/kg) once a day. MPI and AA5 imaging were performed using micro-SPECT/micro-CT. After in vivo imaging, aortas were explanted to acquire ex vivo images and calculate percent injected dose per gram (%ID/g) uptake. Histological and immunohistochemical characterization and extent of MMP and apoptosis were evaluated in representative aortic samples. Both MPI and Annexin uptake were clearly visualized in the atherosclerotic lesions by noninvasive imaging; No uptake were observed after diet withdrawal, fluvastatin, and in normal control groups. %ID/g MPI and AA5 uptakes in the atherosclerotic lesions (0.09 ± 0.02%, 0.03 ± 0.01%) were significantly higher than the uptake in control abdominal aorta (0.014 ± 0.004%, 0.0007 ± 0.0002%; p<0.0001). The quantitative uptake in fluvastatin (0.053 ± 0.013%, 0.02 ± 0.01%; p<0.05) and diet withdrawal (0.047 ± 0.005%, 0.02 ± 0.004%; p<0.05) groups were statistically significantly lower compared to diet uninterrupted group. There were significant direct relationship betweem MPI and AA5 uptake in all experimental group (r=0.62, p<0.0001). The decrease in the tracer uptake maintained the relationship in the fluvastatin group (r=0.62, p<0.0001) but became less apparent in the diet withdrawal (r=0.24, p<0.05). Histopathological and immunohisto-chemical studies revealed a significant correlation of both MPI and Annexin uptake with macrophage infiltration, MMP-2, 9 expression and the extent of apoptosis. Dual imaging with MPI and AA5 showed good correlation between apoptosis and MMP expression except diet withdrawal group.

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