Table 2.
AS biomarkers used in molecular imaging
| Biomarkers | Molecular imaging probes | Imaging technique | Author | References |
|---|---|---|---|---|
| VCAM-1 | Validate an (18)F-labeled small VCAM-1 affinity ligand and demonstrate the feasibility of imaging VCAM-1 expression by PET–CT | PET–CT MRI |
Nahrendorf et al | 11, 28–30, 114 |
| Lipids | sIVPA imaging identifies lipids in human coronary AS plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components | sIVPA | Jansen et al | 31 |
| OSEs | Manganese (Mn(II)) molecular imaging probes targeting to OSEs with oxidation-specific antibodies MDA2 and IK17 | MR | Briley-Saebo et al | 35 |
| Macrophages CD204 | Using anti-CD204 monoclonal IgG | MRI | Amirbekian et al | 40–44 |
| LOX-1 | Imaging probe consisting of liposomes loaded with LOX-1 antibody or nonspecific immunoglobulin G | SPECT/CT and MR | Li et al | 47 |
| LOX-1 antibody conjugated to USPIO nanoparticles could take the probe to vulnerable plaques, which will be verified by colocalization with vulnerable plaque biomarker | MRI | Wen et al | 50 | |
| Stable plaque | Using the novel CD80-specific probe discriminated the stable ones from vulnerable atherosclerotic plaques | PET | Muller et al | 51 |
| MMP | Synthesized radiolabeled MPIs | Radionuclide imaging | Hartung et al | 58 |
| A kind of MPI labeled with 99mTc could be used as an MMP-targeted tracer | Micro-SPECT | Razavian M et al | 59 | |
| Using broad-spectrum MMP inhibitor HO-CGS 27023A, labeled with 123I or 125I image MMP activity | Scintigraphy | Schafers et al | 60 | |
| PS | Utilizing Annexin A5 (like 99mTc-annexin A5) to target PS, which was highly taken up in plaque rich in macrophages | SPECT/CT | Zhao et al | 68–70 |
| Apoptosis (liposomes contained PS) | Utility of paramagnetic Gd-PS | Fluorescence plate reader and MRI | Maiseyeu et al | 74 |
| Caspase activity | Utilizing a peptide-based caspase inhibitor for quantification of caspase activity | PET | Hight et al | 75 |
| Matrix remodeling | Using an elastin-specific contrast agent to assess vascular remodeling for the prediction of vulnerable plaques | MRI | Phinikaridou et al | 77 |
| αvβ3 integrina | Expression of αvβ3 integrin by vasa vasorum was imaged at 1.5 T in cholesterol-fed rabbit aortas using integrin-targeted paramagnetic nanoparticles that incorporated fumagillin at 0 or 30 µg/kg | MRI | Winter et al | 76 |
| NGALa | It is highly expressed in plaques and associated with increased MMP-9 activity. Thus, enhancement of MR images on the abdominal aorta of ApoE(−/−)/eNOS(−/−) mice and colocalization of micelles, macrophages, and NGAL/24p3 were observed at 72 h after injection of NGAL/24p3-targeted micelles | MRI | te Boekhorst et al | 52 |
| VEGFa | Molecular near-infrared fluorescent imaging with an engineered Cy5.5-labeled single-chain VEGF tracer (scVEGF/Cy) to detect VEGF receptors and vascular remodeling in human coronary artery grafts by molecular imaging | Near-infrared fluorescent imaging | Zhang et al | 78 |
| CD40a | A synthetic peptide corresponding with the phage insert NP31 displayed nanomolar affinity for CD40 and this design of a novel, selective peptide ligand for CD40 by phage display examined | Truncation and alanine scan studies | Yu et al | 55 |
Notes:
The biomarker of AS, which has brighter future as potential targets for molecular imaging. Gd-PS, gadolinium liposomes enriched with PS.
Abbreviations: AS, atherosclerosis; CT, computed tomography; LOX-1, Lectin-like oxidized low-density lipoprotein receptor-1; MMP, matrix metalloproteinase; MPIs, MMP inhibitors; MR, magnetic resonance; MRI, magnetic resonance imaging; NGAL, neutrophil gelatinase-associated lipocalin; OSEs, oxidation-specific epitopes; PET, positron emission tomography; PS, phosphatidylserine; sIVPA, spectroscopic intravascular photoacoustics; SPECT, single photon emission CT; USPIO, ultrasmall superparamagnetic iron oxide; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular endothelial growth factor.