BACKGROUND: In this study, we report on the use of a new, bolus-injectable, carboxymethyl dextran-based magnetic nanoparticle (MNP), ferumoxytol, to improve detection in loco-regional lymph nodes by magnetic resonance imaging (MRI). Methods: This preliminary study was performed as a prospective, single-center, open label pilot study to determine the magnitude of nodal MRI signal changes and to determine the optimal time points for imaging following intravenous (IV) bolus injection of the MNP. The study group consisted of 10 patients, all of whom were diagnosed with prostate cancer before any systemic therapy. RESULTS: All 10 patients had lymph nodes evaluated by histopathology. Of the evaluated 26 lymph nodes, 20 were benign and 6 were malignant. The mean short-axis diameter of benign lymph nodes was 6 mm and the mean short-axis diameter of malignant lymph nodes was 7 mm. Following IV administration, there was a significant change in mean signal-to-noise ratio (SNR) of benign lymph nodes (P < .0001) whereas there was little change in the mean SNR of malignant nodes (P = .1624). No adverse events were encountered. CONCLUSION: Ferumoxytol is safe and, at the appropriate circulation interval, modulates nodal signal intensity, allowing for identification of malignant nodal involvement by MRI.