Dataset Information

Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo.

ABSTRACT:

Purpose

To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947.

Materials and methods

The Animal Care and Use Committee approved all experiments. P947 was synthesized by attaching a gadolinium chelate (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) to a peptide that specifically binds MMPs. Scrambled form of P947 (P1135) was synthesized by replacing the targeting moiety of P947 with a scrambled peptide lacking the ability to bind MMPs. P947, P1135, and gadoterate meglumine were injected into atherosclerotic apolipoprotein E-deficient and wild-type mice. The aortic MR imaging enhancement produced by the contrast agents was measured at different times and was compared by using one-way analysis of variance. MMP expression was investigated in the aortas by using MMP immunostaining and in situ MMP zymography. A fluorescent form of P947 (Eu-P947) was synthesized to compare the in vivo distribution of the contrast agent (Eu-P947) with specific MMP immunofluorescent staining.

Results

MMP-targeted P947 facilitated a 93% increase (P < .001) in MR image signal intensity (contrast-to-noise ratio [CNR], 17.7 compared with 7.7; P < .001) of atherosclerotic lesions in vivo. Nontargeted P1135 (scrambled P947) provided 33% MR image enhancement (CNR, 10.8), whereas gadoterate meglumine provided 5% (CNR, 6.9). Confocal laser scanning microscopy demonstrated colocalization between fluorescent Eu-P947 and MMPs in atherosclerotic plaques. Eu-P947 was particularly present in the fibrous cap region of plaques.

Conclusion

P947 improved MR imaging for atherosclerosis through MMP-specific targeting. The results were validated and provide support for further assessment of P947 as a potential tool for the identification of unstable atherosclerosis.

SUBMITTER: Amirbekian V

PROVIDER: S-EPMC2674553 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Publications

Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo.

Amirbekian Vardan V Aguinaldo Juan Gilberto S JG Amirbekian Smbat S Hyafil Fabien F Vucic Esad E Sirol Marc M Weinreb David B DB Le Greneur Soizic S Lancelot Eric E Corot Claire C Fisher Edward A EA Galis Zorina S ZS Fayad Zahi A ZA

Radiology 20090501 2

<h4>Purpose</h4>To evaluate the capability of P947, a magnetic resonance (MR) imaging contrast agent that molecularly targets matrix metalloproteinases (MMPs), to aid detection and imaging of MMPs in atherosclerotic lesions in vivo; its specificity compared with that of P1135; expression and distribution of MMPs in atherosclerotic vessels; and in vivo distribution and molecular localization of fluorescent europium (Eu) P947.<h4>Materials and methods</h4>The Animal Care and Use Committee approved ...[more]

PMID: 19224894

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Project description:Purpose To implement a magnetic resonance (MR) imaging protocol to measure intracranial atherosclerotic disease (ICAD) in a population-based multicenter study and report examination and reader reliability of these MR imaging measurements and descriptive statistics representative of the general population. Materials and Methods This prospective study was approved by the institutional review boards and compliant with HIPAA. Atherosclerosis Risk in Communities (ARIC) study participants (n = 1980) underwent brain MR imaging from 2011 to 2013 at four ARIC sites. Imaging included three-dimensional black-blood MR imaging and time-of-flight MR angiography. One hundred two participants returned for repeat MR imaging to estimate examination and reader variability. Plaque presence according to vessel segment was recorded. Quantitative measurements included lumen size and degree of stenosis, wall and/or plaque thickness, area and volume, and normalized wall index for each vessel segment. Reliability was assessed with percentage agreement, κ statistics, and intraclass correlation coefficients. Results Of the 1980 participants, 1755 (mean age, 77.6 years; 1026 women [59%]; 1234 white [70%]) completed examinations with adequate to excellent image quality. The weighted ICAD prevalence was 34.4% (637 of 1755 participants) and was higher in men than women (38.5% [302 of 729 participants] vs 31.7% [335 of 1026 participants], respectively; P = .012) and in African Americans compared with whites (41.1% [215 of 518 participants] vs 32.4% [422 of 1234 participants], respectively; P = .002). Percentage agreement of plaque identification per participant was 87.0% (interreader estimate), 89.2% (intrareader estimate), and 89.9% (examination estimate). Examination and reader reliability ranged from fair to good (κ, 0.50-0.78) for plaque presence and from good to excellent (intraclass correlation coefficient, 0.69-0.99) for quantitative vessel wall measurements. Conclusion Vessel wall MR imaging is a reliable tool for identifying and measuring ICAD and provided insight into ICAD distribution across a U.S. community-based population. (©) RSNA, 2016 Online supplemental material is available for this article.

Dataset Information

Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo.

Purpose

Materials and methods

Results

Conclusion

Publications

Atherosclerosis and matrix metalloproteinases: experimental molecular MR imaging in vivo.

Similar Datasets

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