February 27, 2006
Engineered Nanomaterials Provide Two Approaches to Improving Magnetic Resonance
Two groups of investigators in Europe have developed engineered nanoscale materials that enhance images obtained using magnetic resonance (MR) imaging. With further development, these nanomaterials have the potential to improve the detection of early stage cancer.
Walter Backes, M.D., of the Maastricht University Hospital, in Maastricht, The Netherlands, led a group of investigators who evaluated gadolinium-loaded dendrimers as contrast agents for MR imaging. Gadolinium, attached to small organic molecules, has already found wide use as an MR contrast agent, but the small size of these agents limits their use in distinguishing between benign and malignant tumors. Dendrimers, however, are small enough to escape from the leaky blood vessels growing around malignant tumors, but are too large to escape from blood vessels found around benign tumors and in healthy tissue. Dendrimers are highly branched, spherical polymers, and some dendrimers are already under development as nanoscale cancer imaging and therapeutic agents.
Besides their larger size, dendrimers offer another advantage as gadolinium carriers. Because there are many places on the dendrimer structure on which to attach gadolinium ions, it is possible to obtain a greater signal enhancement with dendrimer-based constructs than arises with small organic carriers, which in turn, could increase the sensitivity with which MR could detect the smallest tumors. Indeed, tests in animals found that the minimum detectable concentration for a dendrimer containing 64 gadolinium ions was 100-fold less than with a commercially available gadolinium MR contrast agent. These tests also showed that this dendrimer remained in tumors far longer than the commercial agent, but that it was still cleared from the body through the kidneys in a reasonable amount of time.
Meanwhile, a team of investigators in neighboring France, led by Jean-François Berret, Ph.D., of the CNRS Université Denis Diderot in Paris, has used magnetic iron nanocrystals as the basis for its new MR contrast agent candidate. In their work, published in the Journal of the American Chemical Society, the researchers used a self-assembling polymer to encapsulate multiple iron oxide nanocrystals within a single polymer-coated construct. The resulting nanoparticles have diameters between 70 and 150 nanometers, a size well-suited for tumor imaging, and contain tens to hundreds of iron oxide nanocrystals per polymer-coated nanoparticle.
The researchers found that they could adjust the size of the final nanoparticle through their choice of the exact polymer used for encapsulation. Larger particles, containing greater number of iron oxide nanocrystals, produced a more substantial boost in MR signals. This group of investigators has yet to test these nanoparticles in animals.
The work with gadolinium-loaded dendrimers is detailed in a paper titled, “Evaluation of Gd(III)DTPA-terminated poly(propylene imine) dendrimers as contrast agents for MR imaging.” Investigators from the Eindhoven University of Technology in Eindhoven, The Netherlands, also participated in this study. An abstract of this paper is available through PubMed.
The work with polymer-encased nanoparticle clusters is detailed in a paper titled, “Controlled clustering of superparamagnetic nanoparticles using block copolymers: design of new contrast agents for magnetic resonance imaging.” Investigators from the Université Pierre et Marie Curie, in Paris, and the Centre de Recherches d’Aubervilliers, in Aubervilliers, France, also participated in this study. An abstract of this paper is available through PubMed.