Molecular Imaging of Cardiovascular Disease

Abstract

Molecular imaging aims at sensing specific molecular targets, fundamental biological processes, and certain cell types in living subjects. An integrative discipline rooted in the biological, chemical, and imaging sciences, molecular imaging has broad applications in biology and drug discovery1–5 and increasingly within cardiovascular disease.6–12 Before discussing key factors spurring the growth of this field, we first briefly review 2 essential components of this technology: imaging agents and imaging hardware. Molecular imaging requires highly sensitive and specific imaging agents. Such agents incorporate 2 key factors: (1) a signal detection compound and the corresponding imaging hardware platform and (2) an affinity ligand that recognizes the intended molecular or cellular target. Favorable targets include those with established biological and clinical importance in a disease of interest, as well as targets with inherent signal amplification potential such as internalizing receptors or enzymes. Inaccessible and low-abundance targets (DNA, RNA, sparsely expressed proteins) present greater challenges, particularly in a noninvasive, clinical setting. Signal detection compounds include radioisotopes for positron emission tomography (PET) and single-photon-emission computed tomography (SPECT) imaging, paramagnetic (gadolinium)/superparamagnetic (iron oxide) agents for magnetic resonance imaging (MRI), fluorochromes for near-infrared fluorescence imaging, and microbubbles for ultrasound imaging. Certain agents can exhibit unique physical changes favorable for signal amplification when spaced close together (eg, quenching of fluorochromes13–18 or augmented relaxivity of magnetic substrates19–21). These tags can form the basis of imaging agents with inherent chemical amplification capabilities. Amplification strategies generally enable higher target-to-background ratios, a key strategy for developing sufficiently sensitive agents for clinical use. Affinity ligands confer molecular or cellular specificity for the target of interest. The application of novel ligand screening methods, emerging new chemistries for conjugation and signal amplification, and nanotechnology have fostered substantial growth in ligand development. From a clinical perspective, qualities of an ideal ligand include (1) …