Ultrasound Molecular Imaging Contrast Agent Binding to Both E- and P-Selectin in Different Species

Bettinger, Thierry; Bussat, Philippe; Tardy, Isabelle; Pochon, Sibylle; Hyvelin, Jean-Marc; Emmel, Patricia; Henrioud, Sylvie; Biolluz, Nathalie; Willmann, Jürgen K.; Schneider, Michel; Tranquart, F.

doi:10.1097/rli.0b013e31825cc605

Cited by 53 publications

(48 citation statements)

References 43 publications

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“…In this model, ethanol breaks the physical barrier of the intestine, allowing TNBS to haptenize intestinal autologous or microbiota proteins. This results in a T-cell-dependent mucosal immune response and transmural infiltration of neutrophils (10,25). We observed that the volume of ethanol can be substantially reduced to 0.8 mL (compared with 40 mL, as published previously [22,23]), which caused moderate-to-severe TNBS-mediated inflammation with minimal discomfort to the animals.…”

Section: Discussionsupporting

confidence: 54%

“…This technique has been used to quantify inflammation in small-animal models of IBD (8,9). Leveraging the natural pathway of leukocyte rolling on inflamed vascular endothelial cells, a clinically translatable, dual-targeted contrast agent (10,11) specific for the leukocyte adhesion molecules P-and E-selectin has been shown to enable accurate quantification of inflammation in a murine model of chemically induced colitis (12). Furthermore, in an intra-animal cross-modality comparison (12), dual-selectin-targeted US signal correlated well quantitatively with fluorodeoxyglucose uptake at positron emission tomography/CT in murine colitis.…”

Section: Fundingmentioning

confidence: 99%

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Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

et al. 2015

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Purpose:To evaluate the feasibility and reproducibility of ultrasonography (US) performed with dual-selectin-targeted contrast agent microbubbles (MBs) for assessment of inflammation in a porcine acute terminal ileitis model, with histologic findings as a reference standard. Materials and Methods:The study had institutional Animal Care and Use Committee approval. Acute terminal ileitis was established in 19 pigs; four pigs served as control pigs. The ileum was imaged with clinical-grade dual P-and E-selectin-targeted MBs (MB Selectin ) at increasing doses (0.5, 1.0, 2.5, 5.0, 10, and 20 3 10 8 MB per kilogram of body weight) and with control nontargeted MBs (MB Control ). For reproducibility testing, examinations were repeated twice after the MB Selectin and MB Control injections. After imaging, scanned ileal segments were analyzed ex vivo both for inflammation grade (by using hematoxylin-eosin staining) and for expression of selectins (by using quantitative immunofluorescence analysis). Statistical analysis was performed by using the t test, intraclass correlation coefficients (ICCs), and Spearman correlation analysis. Results:Imaging signal increased linearly (P , .001) between a dose of 0.5 and a dose of 5.0 3 10 8 MB/kg and plateaued between a dose of 10 and a dose of 20 3 10 8 MB/ kg. Imaging signals were reproducible (ICC = 0.70), and administration of MB Selectin in acute ileitis resulted in a significantly higher (P , .001) imaging signal compared with that in control ileum and MB Control . Ex vivo histologic grades of inflammation correlated well with in vivo US signal (r = 0.79), and expression levels of both P-selectin (37.4% 6 14.7 [standard deviation] of vessels positive; P , .001) and E-selectin (31.2% 6 25.7) in vessels in the bowel wall of segments with ileitis were higher than in control ileum (5.1% 6 3.7 for P-selectin and 4.8% 6 2.3 for E-selectin). Conclusion:Quantitative measurements of inflammation obtained by using dual-selectin-targeted US are reproducible and correlate well with the extent of inflammation at histologic examination in a porcine acute ileitis model as a next step toward clinical translation.q RSNA, 2015

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Section: Discussionsupporting

confidence: 54%

Section: Fundingmentioning

confidence: 99%

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

et al. 2015

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“…Thrombogenicity and complement activation may still be given even if VCAM-1 expression levels have been normalized. Therefore, other adhesion molecules involved in leukocyte recruitment and transendothelial migration, such as P-selectin, 37,38 should be investigated in future studies as well, to provide evidence for a functional endothelial recovery. Second, streptavidin-coated MBs are not clinically translatable, nor is the use of biotinylated antibodies.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup

Curaj

Fokong

et al. 2015

ATVB

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Objective— Cardiovascular interventions induce damage to the vessel wall making antithrombotic therapy inevitable until complete endothelial recovery. Without a method to accurately determine the endothelial status, many patients undergo prolonged anticoagulation therapy, denying them any invasive medical procedures, such as surgical operations and dental interventions. Therefore, we aim to introduce molecular ultrasound imaging of the vascular cell adhesion molecule (VCAM)-1 using targeted poly- n -butylcyanoacrylate microbubbles (MB VCAM-1 ) as an easy accessible method to monitor accurately the reendothelialization of vessels. Approach and Results— ApoE −/− mice were fed with an atherogenic diet for 1 and 12 weeks and subsequently, endothelial denudation was performed in the carotid arteries using a guidewire. Molecular ultrasound imaging was performed at different time points after denudation (1, 3, 7, and 14 days). An increased MB VCAM-1 binding after 1 day, a peak after 3 days, and a decrease after 7 days was found. After 12 weeks of diet, MB VCAM-1 binding also peaked after 3 days but remained high until 7 days, indicating a delay in endothelial recovery. Two-photon laser scanning microscopy imaging of double fluorescence staining confirmed the exposure of VCAM-1 on the superficial layer after arterial injury only during the healing phase. After complete reendothelialization, VCAM-1 expression persisted in the subendothelial layer but was not reachable for the MB VCAM-1 anymore. Conclusion— Molecular ultrasound imaging with MB VCAM-1 is promising to assess vascular damage and to monitor endothelial recovery after arterial interventions. Thus, it may become an important diagnostic tool supporting the development of adequate therapeutic strategies to personalize anticoagulant and anti-inflammatory therapy after cardiovascular intervention.

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“…Molecular US imaging has been successfully applied to inflammations including inflammatory bowel diseases, myocardial ischemia, arthrosclerosis, and rejection in cardiac transplantation. Bettinger developed P-selectin glycoprotein-functionalized MBs (MBrPSGL-Ig) [60]. The adhesion efficiency of MBrPSGL-Ig constructs under static or flow conditions and molecular imaging studies were performed in the rat inflammatory model by intravenous injection of MBs with monitoring the accumulation of targeted MBs in the muscle.…”

Section: Inflammationmentioning

confidence: 99%

Section: Inflammationmentioning

confidence: 99%

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

Wang

et al. 2016

Applied Sciences

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Microbubbles as traditional ultrasound contrast agents have seen tremendous developments and bio-applications in the past decades. Due to their outstanding performance, advanced microbubbles as a multifunctional platform combining both imaging and therapy have been increasingly attracting attention. Associated with ultrasound-mediated stimuli, targeting drug transportation with high precision can be established and, as a consequence, a synergistic treatment strategy may prevail, which implies a bright perspective for this brand-new technology. This perspective article will summarize the latest developments on the advanced microbubbles, and review their emerging biomedical applications for the vast community of both applied ultrasound and functional ultrasound-based materials.

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Ultrasound Molecular Imaging Contrast Agent Binding to Both E- and P-Selectin in Different Species

Cited by 53 publications

References 43 publications

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

Quantitative Assessment of Inflammation in a Porcine Acute Terminal Ileitis Model: US with a Molecularly Targeted Contrast Agent

Noninvasive Molecular Ultrasound Monitoring of Vessel Healing After Intravascular Surgical Procedures in a Preclinical Setup

Advanced Microbubbles as a Multifunctional Platform Combining Imaging and Therapy

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