Chemistry Reference
In-Depth Information
nanopartIculate MrI contrast agents
Juan Gallo and
Department of Chemistry, Imperial College London, London, UK
Nicholas J. Long
9.1
IntroductIon
Nanotechnology is destined to play a major role in future medicine. One of the most advanced examples of nanotechnology
in biomedicine is the use of magnetic nanoparticles. Commercially available formulations of iron oxide nanoparticles are
currently approved for their application in hospitals to diagnose liver carcinomas by magnetic resonance imaging (MRI).
This detection is based on the unspecific accumulation of the contrast agent in the liver as a 'detoxifying' organ, but it cannot
easily be extended to the detection or treatment of other tissues. However, due to the excellent performance of the nanopar-
ticles in this specific example, it has encouraged further research in this general field of nanotechnology [1-4]. Most of the
studies are based on the same kind of iron oxide nanoparticles or on their derivatives (ferrites), because they have proven
themselves to be a powerful starting point due to their lack of toxicity, stability, biodegradability, and acceptable contrast
enhancement [5]. Other magnetic materials, such as FeCo or FePt [6], have also been tested as possible contrast agents,
although they present different issues, as will be discussed later in the chapter.
All the materials mentioned so far act as T
2
contrast agents. This means that they can be detected by MRI because they
create their own magnetic field that disturbs the field from the instrument, negating the signal from their surroundings (the
final effect is a darkening of the image in the areas where the T
2
contrast agent is present). However, these contrast agents
present several inherent problems [7]. First, their effect on tissues results in labelled areas appearing as hypointense regions,
sometimes making it difficult to distinguish labelled areas from pathogenic conditions, for example, bleeding. In addition,
the high susceptibility of these kinds of agents perturbs the magnetic field of the neighbouring unlabelled tissues in what is
called the
susceptibility artefact
or
blooming effect
, making it difficult to identify the exact state of the lesion [8]. These facts
are the reason why researchers have also started to examine T
1
nanoparticle-based contrast agents [7, 9]. T
1
contrast agents
are already in clinical use but mainly in the form of Gd chelates. As nanoparticles, the main two T
1
-based materials tested to
date have been gadolinium(III) oxide and manganese oxide.
In general, the use of nanoparticles in medicine presents several advantages over the use of traditional chemical struc-
tures. Nanoparticles can be used as beacons over which different molecules with different roles can be attached. In this way
a nanoparticle can carry, on one hand, a targeting molecule toward a diseased area, and on the other a drug to treat this dis-
ease, while the metallic core of the nanoparticle can provide the means for detection. Also, nanoparticle structures are
capable of carrying hundreds to thousands of ligand molecules that can result in an enhanced local concentration of the drug
once it reaches the target. In the same way, multivalent presentation of ligands on the surface of the nanoparticles allows for
the use of molecules with low affinity toward their target (i.e., carbohydrates), widening the range of options to achieve
specific labelling.
