Molecular Imaging of Atherosclerotic Plaque Characteristics

Molecular imaging has emerged as a transformative approach for the non-invasive characterisation of atherosclerotic plaques, offering insights into cellular and biochemical activities that cannot be discerned by anatomical imaging alone. By targeting specific molecular signatures—such as inflammatory macrophages, neovascular endothelium and matrix remodelling—techniques including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) can visualise plaque vulnerability and guide personalised risk assessment. Recent advances have centred on the development of targeted probes and multimodal platforms that combine high sensitivity with detailed morphological context. These approaches enable the detection of macrophage subtypes via receptor-directed tracers, the identification of microvessel proliferation through integrin-binding peptides and the quantification of disease activity using nanometre-scale particles. Collectively, these innovations promise to refine prognostic stratification, monitor therapeutic response and accelerate the translation of anti-atherosclerotic interventions.

Research from Nature Portfolio

A novel fluorine-18-labelled polyglucose nanoparticle, known as Macroflor, has been designed for PET imaging of macrophage density in inflamed plaques. Its small size permits rapid renal clearance, and in preclinical models Macroflor uptake closely tracks macrophage burden in both myocardial infarcts and atherosclerotic lesions. When combined with MRI, Macroflor PET/MRI delineates dynamic changes in inflammatory cell populations and resolves evolving plaque activity.

Gold-coated iron oxide nanoparticles, functionalised with an antibody against the CD163 macrophage receptor, have been employed as an MRI probe to detect haemorrhagic and inflammatory plaque sites. In murine atherosclerosis, these particles accumulate selectively in CD163-expressing macrophages, yielding a pronounced signal change that correlates with local gene expression of inflammatory markers, thus enabling the identification of high-risk plaques.

A dimeric RGD peptide radiotracer targeting integrin αvβ3 has been developed for SPECT/CT imaging of plaque neovascularisation. In murine models, the dimer probe shows enhanced binding to αvβ3-rich microvessels compared with monomeric analogues, highlighting regions of active angiogenesis and thin-cap fibroatheroma characteristics. This approach offers a sensitive tool for capturing neovessel abundance—a key feature of vulnerable plaques.

Molecular Imaging of Atherosclerotic Plaque Characteristics publication trend

The graph below shows the total number of articles in molecular imaging of atherosclerotic plaque characteristics across all publications each year (not limited to Nature Index journals).

Technical terms

Molecular imaging: Techniques that visualise cellular and molecular processes in vivo.

Positron emission tomography (PET): A nuclear imaging method that detects radioactive tracers emitting positrons.

Single-photon emission computed tomography (SPECT): Imaging based on gamma-ray-emitting isotopes to map molecular targets.

Nanoprobe: A nanoscale agent designed to bind specific biological markers and produce detectable signals.

Macroflor: A fluorine-18-labelled polyglucose nanoparticle for imaging macrophage density.

CD163: A macrophage scavenger receptor indicative of anti-inflammatory or haemorrhagic plaque regions.

Integrin αvβ3: A receptor upregulated on neovessel endothelium within vulnerable plaques.

References

1. Molecular imaging nanoprobes and their applications in atherosclerosis diagnosis. Theranostics (2024).
2. Long-axial field-of-view PET/CT for the assessment of inflammation in calcified coronary artery plaques with [68 Ga]Ga-DOTA-TOC. European Journal of Nuclear Medicine and Molecular Imaging (2023).
3. Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease. Nature Communications (2017).
4. Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI. Scientific Reports (2015).
5. SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides. Scientific Reports (2015).