Elsevier

Journal of Nuclear Cardiology

Volume 11, Issue 6, November–December 2004, Pages 733-743
Journal of Nuclear Cardiology

From bench to imaging
Magnetic resonance molecular imaging with nanoparticles

https://doi.org/10.1016/j.nuclcard.2004.09.002Get rights and content

Molecular imaging agents are extending the potential of noninvasive medical diagnosis from basic gross anatomic descriptions to complicated phenotypic characterizations based on the recognition of unique cell surface biochemical signatures. Although originally the purview of nuclear medicine, molecular imaging is now a prominent feature of most clinically relevant imaging modalities, in particular magnetic resonance (MR) imaging. MR nanoparticulate agents afford the opportunity not only for targeted diagnostic studies but also for image-monitored site-specific therapeutic delivery, much like the “magic bullet” envisioned by Paul Erhlich 100 years ago. Combining high-resolution MR molecular imaging with drug delivery will facilitate verification and quantification of treatment (ie, rational targeted therapy) and will offer new clinical approaches to many diseases.

Section snippets

The NMR phenomenon

An understanding of MR contrast agents is founded upon a rudimentary understanding of MR imaging and the NMR (nuclear magnetic resonance) phenomenon. The basic principle of NMR states that intrinsic angular momentum or spins of protons (ie, hydrogen nuclei) and electrons, 1, 2 when placed in a strong external magnetic field (B0), orientate themselves either parallel (ie, spin up) or antiparallel (ie, spin down) to B0. The overall impact, which is a function of B0, is minute, about 0.01 to 0.1

Passive targeting

Contrast agents can concentrate within a pathologic site by either passive or active targeting mechanisms. Passive targeting agents primarily highlight phagocytic cells and organs naturally responsible for particle clearance within the body. Macrophages, the primary phagocytic cell type responsible for the removal of foreign materials, originate in the bone marrow as pre-monocytes, circulate as monocytes, and localize into connective tissue (histiocytes), liver (Kupffer’s cells), lung (alveolar

Iron oxide–based agents

Superparamagnetic metals, such as iron oxides, exert influence well beyond their immediate size, which accounts for their ease of detection on T1/T2 or highly T2-weighted images. A wide variety of iron oxide–based nanoparticles have been developed that differ in hydrodynamic particle size and surface coating material (dextran, starch, albumin, silicones). 4 In general terms, these particles are categorized based on nominal diameter into superparamagnetic iron oxides (SPIOs) (50-500 nm) and

Paramagnetic gadolinium-based nanoparticles

USPIOs provide adequate circulation time for tissue penetration but also require significant time, usually 24 hours, for sufficient background signal clearance. Because these agents create an extended image void, proximate anatomy surrounding key targeted points of interest maybe obscured. This is particularly manifested in high-resolution imaging. The interest in paramagnetic contrast agents for molecular imaging reflects an alternative desire to create a “bright” contrast signal rapidly,

Summary

MR is emerging as an advantageous technique for molecular imaging, given its high spatial resolution and unique capability to elicit both anatomic and physiologic information simultaneously. Superparamagnetic agents take advantage of the wide-ranging effects of susceptibility artifacts produced by iron oxides, which appear as dark contrast voids with T2-weighted imaging. Alternatively, development of ultraparamagnetic nanoparticles or liposomes, which carry high paramagnetic payloads, exert a

Acknowledgment

The authors have indicated they have no financial conflicts of interest.

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