Superparamagnetic iron oxide nanoparticles (SPION)-based magnetic resonance imaging is a powerful, noninvasive tool in biomedical imaging. The recent embedding of SPIO in nanoencapsulations that had different controllable surface properties has now made it possible to use SPIO in the imaging of metabolic processes. The two major issues to realize maximized and selective SPIO cancer targeting are the minimization of macrophage uptake and the preferential binding to cancerous cells over healthy neighbor cells. The utility of SPIO has been shown in clinical applications using a series of marketed SPION-based contrast agents. Applications have ranged from detecting inflammatory diseases to the specific identification of cell surface markers expressed on tumors. This review focuses on iron-oxide-based nanoparticles, to include the physiochemical properties of SPION surface engineering and its synthetic methods as well as SPIO imaging applications and specifically targeted SPIO conjugates (e.g. targeted probes) for labeling cancerous, cell-surface molecules. As a specific application of this technology, we discuss its use in the imaging of pancreatic duct adenocarcinoma in addition to its potential for use in early diagnosis through targeted strategies.