< Back to previous page

Project

Integrated magnetic nanoparticle-enabled imaging of therapeutic cells: IMAGINE (R-1945)

Disease starts at the biomolecular and cellular level and on subnanometer length scales. The holy grail of medicine is diagnostics and intervention on that scale and biocompatible nanosized particles have emerged as suitable multifunctional tools to reach this goal. In vivo diagnostic and therapeutic methods can benefit highly from every new development in nanoparticle research, one example is the emerging field of cell-based therapies, where researchers need to follow cells for hours and even weeks after they are introduced in the body in order to assess their effectiveness. Various experimental studies have proven the suitability of magnetic nanoparticles and Magnetic Resonance Imaging (MRI) for monitoring cell migration in vivo. Hereby, cells are usually loaded with iron oxide nanoparticles that generate a pronounced dark contrast (hypointensity in T2 and T2*-weighted MR images). Compared to microscopic methods, MRI has the advantage to study the temporal evolution of biological processes in individuals non-invasively. Compared to other molecular imaging methods (e.g. nuclear techniques (PET, SPECT), optical imaging (BLI) or ultrasound techniques), MRI has the advantage of a very high resolution (as high as 20 ƒÝm isotropic). Current commercial MRI contrast agents, however, have rather poor sensitivity and specificity and lack the ability to quantify images. The engineered superparamagnetic nanocrystals have therefore the potential to dramatically improve current diagnostic techniques. This project aims to develop magnetic nanoparticle crystals with physicochemical properties tailored for in vivo diagnostic MR imaging and cell tracking following the ex-vivo labeling of cells. Desirable properties from such nanoparticles are stronger signal intensity using a smaller number of particles, better and more specific cellular uptake, the potential to be utilized for quantification and non-toxicity, improved specificity and stability in time. Such requirements can be met by tuning the magnetic composition, the physical size and geometry, the chemical and biofunctional coatings, polymeric/silica based core-shell thickness and/or lipidic coating techniques. Such nanoparticle development effort also requires co-development of analytical techniques to assess the properties of these novel materials. To reach this aim, we need to develop diagnostic magnetic nanoparticle imaging/tracking methods to reach high sensitivity and specificity. Whereas current MRI diagnostic imaging techniques are optimized to provide maximal tissue contrast, the same instruments can be tuned to be sensitive towards information on the magnetic particles. Such imaging method can be used for sensitive stem cell tracking. Stem cells, with the capacity to differentiate into different types of cells and finally tissue, raise the hope of cell-based regenerative medicine for many diseases (such as ischemic heart disease, neural disease, cancer, and many other disorders). As determining the fate of stem cells or their lineage committed progeny transplanted in vivo will be of importance, stem cell labeling and imaging represents an excellent model system in order to improve particle based tracking methods. Novel cell labeling techniques as well as the potential to semi-quantify the number of implanted cells over time will improve the understanding of underlying mechanisms (cellular uptake, migration of the cells to the target organ, unwanted migration of the cells) and assess the success of therapies non-invasively in every individual thereby guiding the translation of experimental therapies into the clinic. In addition, the well studied migratory potential of stem and progenitor cells towards a site of injury (e.g. stroke, trauma or tumor) can be utilized for the delivery of drugs. The project will take advantage of this by evaluating the bystander suicide killing effect of genetically modified stem cells and their progeny on tumors. Hereby, the therapy will be initiated by to administration of a pro-drug after evaluation of the biodistribution of the labeled, implanted stem cells using in vivo MRI. The image guided therapeutic approach will allow for precise administration of the pro-drug. It should be noted that insights gained using stem cells will likely be useful in other, if not all, areas of cell based therapy. Finally, diagnostic imaging tools can be realized much cheaper and more compact than today if they are improved with the utilization of more sensitive magnetic nanoparticles and if the high magnetic fields used today can be substituted by cheaper systems. This can pave the way towards small non-invasive diagnostic imaging and monitoring devices at the bedside, providing us with continuous reports from inside the body.
Date:1 Feb 2009 →  31 Jul 2012
Keywords:CELL LABELING TECHNIQUES, CELL TRACKING, DIAGNOSTIC MR IMAGING, MAGNETIC NANOPARTICLE CRYSTALS
Disciplines:Basic sciences, Clinical sciences, Translational sciences