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

Scientific Reports
Darren G WoodsideAnanth Annapragada

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 α4β1(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-targete...Continue Reading

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Citations

Apr 3, 2020·Pharmacology Research & Perspectives·Felix H ZakirovAlexander N Orekhov
Apr 8, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jooneon ParkNicole F Steinmetz
Nov 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Armita Mahdavi GorabiAmirhossein Sahebkar
Feb 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tobias LenzMichael Joner
Jan 12, 2021·Advanced Drug Delivery Reviews·Jun ChenHo-Wook Jun
Mar 7, 2021·Biomedicines·Kristina AndelovicAlma Zernecke
Aug 12, 2021·British Journal of Pharmacology·Neil MacRitchiePasquale Maffia

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
fluorescence imaging
saturation binding
FCS

Software Mentioned

GraphPad Prizm
Osirix
Prizm Software

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