“Optimized nanoparticles can be used for sensitive bolus tracking in MPI or can be tagged onto antibodies, so that their docking efficiency can then be observed via MPI or MPS.”
Magnetic nanoparticles that have the attribute of being manipulated by magnetic fields are a current hot research topic due to their potential benefits for therapeutic applications, imaging and biomedicine. This significant potential is driving developments in the field of Magnetic Particle Imaging (MPI), with producers of magnetic nanoparticles keen to exploit new methods for testing. Only by understanding a particle’s properties and characteristics, from surface chemistry to toxicity, can effective end-systems and solutions be devised.
Prototype of the preclinical MPI scanner. Courtesy: Philips Research Hamburg
One such method already showing great potential from early measurements is the first commercial Magnetic Particle Spectrometer from Bruker, installed at the Physikalisch-Technische Bundesanstalt (PTB) in Berlin. The new system is enabling researchers to characterize and optimize magnetic nanoparticles for use in future MPI experiments as well as to provide quantitative support for magnetic nanoparticle therapies.
In MPI and magnetic particle spectroscopy (MPS), an alternating magnetic field is applied to the magnetic nanoparticles which drive their magnetization into, and out of, saturation. Fourier transforming their signal provides spectra that yield the harmonics of the excitation frequency. The Bruker magnetic particle spectrometer allows the drive field strength to be varied between 0.05 and 25 mT. Increasing the drive field strength has the effect of driving the magnetic nanoparticles further towards saturation and leads to a greater signal of the higher harmonics in transformed spectrum. Figure 1 (below) shows how the third harmonic of samples of Resovist® [Bayer Schering Pharma] and Feraheme® [AMAG Pharmaceuticals, Inc.] increases over the drive field range.
Overlay of MPI images on anatomical MR images of the cardiovascular system taken in a preclinical study. The combined images are the three orthogonal cross sections (only two shown here) showing the blood flow in the left heart chamber and the lung arteries. This picture has been published in the March issue of Physics in Medicine and Biology in 2009 (Volume 54, issue 5).
Optimizing particles
For optimum performance in applications, an optimal iron core diameter and form must be determined for each magnetic particle imager with its specific operation frequency. Initial results have shown, for example, that for the preclinical MPI being developed by Bruker in cooperation with Philips, theoretically an iron core diameter of approximately 30 nm with a slight anisotropy provides the best signal [3]. Commercially available MRI contrast agents have typically smaller mean diameters. The limitations mean that the search is on to find and design optimal MPI particles.
Optimized nanoparticles can be used for sensitive bolus tracking in MPI or can be tagged onto antibodies, so that their docking efficiency can then be observed via MPI or MPS. But even “suboptimal” particles can be of use. Two different antibodies can be labeled with two particles with greatly differing spectral characteristics. By examining the magnetic nanoparticle spectrum of the target tissue, the amount of antibodies that successfully docked can then be determined.
Therapeutic applications can also benefit. In one study, researchers labeled a chemotherapeutic agent with magnetic nanoparticles which were injected into an artery then focused on the desired position within the artery by the application of an external magnetic field.
To simulate such a magnetic nanoparticle distribution within an artery, researchers at the PTB prepared a phantom by printing rectangles of varying magnetic laser printer toner coverage. By sequentially examining pieces of the strip and quantifying the magnetic nanoparticle content using MPS, they could reconstruct the profile of the toner coverage as shown.
In collaboration with Philips Research, Hamburg