S-EPMC5829217 - Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin ?4?1. - OmicsDI

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Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin ?4?1.

ABSTRACT: Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in atherosclerotic plaques, especially in the coronary arteries. To address this, we have developed a clinically relevant system to image overall inflammatory cell burden in plaque. Here, we describe a targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable for magnetic resonance (MR) imaging and binds with high affinity and selectivity to the integrin ?4?1(very late antigen-4, VLA-4), a key integrin involved in recruiting inflammatory cells to atherosclerotic plaques. This liposomal contrast agent has a high T1 relaxivity (~2?×?10⁵?mM^-1s^-1 on a particle basis) resulting in the ability to image liposomes at a clinically relevant MR field strength. We were able to visualize atherosclerotic plaques in various regions of the aorta in atherosclerosis-prone ApoE^-/- mice on a 1 Tesla small animal MRI scanner. These enhanced signals corresponded to the accumulation of monocyte/macrophages in the subendothelial layer of atherosclerotic plaques in vivo, whereas non-targeted liposomal nanoparticles did not demonstrate comparable signal enhancement. An inflammatory cell-targeted method that has the specificity and sensitivity to measure the inflammatory burden of a plaque could be used to noninvasively identify patients at risk of an acute ischemic event.

SUBMITTER: Woodside DG

PROVIDER: S-EPMC5829217 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin α4β1.

Woodside Darren G DG Tanifum Eric A EA Ghaghada Ketan B KB Biediger Ronald J RJ Caivano Amy R AR Starosolski Zbigniew A ZA Khounlo Sayadeth S Bhayana Saakshi S Abbasi Shahrzad S Craft John W JW Maxwell David S DS Patel Chandreshkumar C Stupin Igor V IV Bakthavatsalam Deenadayalan D Market Robert V RV Willerson James T JT Dixon Richard A F RAF Vanderslice Peter P Annapragada Ananth V AV

Scientific reports 20180227 1

Inflammation drives the degradation of atherosclerotic plaque, yet there are no non-invasive techniques available for imaging overall inflammation in atherosclerotic plaques, especially in the coronary arteries. To address this, we have developed a clinically relevant system to image overall inflammatory cell burden in plaque. Here, we describe a targeted contrast agent (THI0567-targeted liposomal-Gd) that is suitable for magnetic resonance (MR) imaging and binds with high affinity and selectivi ...[more]

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