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The theoretically predicted maximum r₂ relaxivity of iron oxide nanoparticles was achieved by optimizing the overall size of ferrimagnetic iron oxide nanocubes. Uniform-sized iron oxide nanocubes with an edge length of 22 nm, encapsulated with PEG-phospholipids (WFION), exhibited high colloidal stability in aqueous media. In addition, WFIONs are biocompatible and did not affect cell viability at concentrations up to 0.75 mg Fe/ml. Owing to the enhanced colloidal stability and the high r₂ relaxivity (761 mM^–1 s^–1), it was possible to successfully perform in vivo MR imaging of tumors by intravenous injection of 22-nm-sized WFIONs, using a clinical 3-T MR scanner.