Superparamagnetic iron oxide nanoparticles as a multimodal contrast agent for up to five imaging modalities

Abstract

labeled nanometer sized colloids are injected sub-dermally or peri-tumourally, and then imaged using a gamma camera/SPECT (before surgery) and a gamma probe (during surgery). A blue dye injected prior to surgery may serve to visualize the SLN intra-operatively. When the SLN is found, it is removed by invasive surgery and cancer infiltration is examined using histology. The lack of precise anatomic information in the scintigraphic images and the non-specificity of the tracer, however, often limit the preoperative planning and the identification of the SLN. Multimodal approaches in the clinic, such as the next generation hybrid systems based on combined MR/PETsystems, are expected to address several of these issues. In the pre-clinical setting, an even faster growing segment for medical imaging‐multimodal systems including optical methods is concurrently emerging. Interestingly, there exist still no commercially available clinical contrast agent that can be used for even two modalities, and research has shown functionality for only a couple imaging modalities at a time. Our aim is to develop novel multimodality contrast agents and methodology for such systems to meet new needs for quantitative and high-resolution imaging. In this perspective, superparamagnetic iron oxide nanoparticles (SPIO-NPs) are emerging as a highly attractive approach. SPIO-NPs can be observed by MRI as signal voids in the MR image and SPIO-NPs have been approved as MRI contrast agents for more than a decade with applications including lymph node detection. We propose the use of SPIO-NPs as a multimodal contrast agent by attaching radionuclides and fluorophores to the surface of the nanoparticles, for, respectively, SPECT, PET, and optical imaging methods. Moreover, the particles also inherently functions as contrast media for a new imaging technique called magnetomotive ultrasound imaging. Thus, the very same particles can be used as a contrast agent for up to five modalities, depending on the type of surface modification. We expect the following improvements for the work-flow of cancer patients undergoing lymph node surgery: • One single injection of tracer, and thereby no timing issues experienced with the dye used today. This means less preparation time prior to surgery, and reduced risk of lymph edema due to excessive removal of colored lymph nodes. • Improved staging due to truly combined information in a PET/MR system including tracer migration analysis.