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Molecular imaging in cardiovascular disease: targets and opportunities

Abstract

The practice of clinical cardiology employs many imaging techniques for diagnosis, risk stratification and therapeutic monitoring. These imaging modalities largely provide anatomical or structural information, and only indirectly reflect underlying molecular events. Molecular imaging techniques report on entities or processes that can be defined at the molecular, as opposed to the anatomical, level. For example, molecular imaging can reveal the expression or activity of a specific protein, the fate or localization of a biomolecule, or the activity of a biological pathway. This Review highlights key processes and molecular targets that are currently being investigated experimentally by molecular imaging probes in vivo. Collectively, these targets have an important role in the development of atherosclerosis and acute plaque rupture, as well as in myocardial disease. Molecular imaging technology is now progressing towards clinical application in humans and has the potential to guide diagnosis, risk assessment and treatment response. Imaging-based surrogate end points could speed the development of new drugs, particularly those with novel mechanisms of action. More broadly, by noninvasively reporting on molecular processes in vivo, molecular imaging can reveal how specific proteins or pathways function in their native context, thus contributing to a systems-level understanding of cardiovascular disease biology.

Key Points

  • The imaging techniques currently used in clinical cardiology predominantly provide structural or anatomical information

  • Molecular imaging probes report on the expression or activity of proteins, biological pathways or cells, such as apoptosis, thrombus formation or stabilization, and cellular metabolism

  • Molecular imaging targets can be engaged by antibodies, peptides, aptamers, or small molecules

  • Existing molecular imaging probes have been widely tested in murine or large-animal models of atherosclerosis or myocardial disease; a small number of probes are being investigated in human trials

  • Unbiased screens for novel imaging probes with no prespecified target could facilitate the discovery of novel imaging agents and targets

  • Targeted molecular imaging probes can contribute to phenotyping of patients, drug development, translational studies, and a systems-level view of cardiovascular disease

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Figure 1: A VCAM1-targeted magnetofluorescent nanoparticle reveals the effect of atorvastatin treatment in apolipoprotein E knockout mice on a high-cholesterol diet.
Figure 2: Design of a cathepsin-activated imaging probe.
Figure 3: Structure and activity of myeloperoxidase-activated probe.
Figure 4: In vivo MRI of human thrombi using a fibrin-targeting peptide conjugated to gadolinium–tetraazacyclododecane tetraacetic acid (EP-2104R).
Figure 5: Synthetic HDL-mimetic nanoparticles.
Figure 6
Figure 7: Use of a metabolic imaging probe (18F-FDG PET) to visualize the effect of therapies targeting metabolic pathways.

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Acknowledgements

S. Y. Shaw acknowledges funding from the NIH and National Heart, Lung and Blood Institute.

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Shaw, S. Molecular imaging in cardiovascular disease: targets and opportunities. Nat Rev Cardiol 6, 569–579 (2009). https://doi.org/10.1038/nrcardio.2009.119

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