The application of ultra-small super-paramagnetic iron oxide nanoparticles (USPIONs) as versatile diagnostic probes for multimodal imaging in biomedicine, including via magnetic resonance imaging (MRI) and positron emission tomography (PET), requires hydrophilic and biocompatible surface coatings. Herein, we describe the development of USPIONs stabilised by octylamine-modified polyacrylic acid (OPA) and the subsequent conjugation of a 64Cu(ii) chelator, N-(4-aminophenyl)-2-[4,7-bis(2-pyridylmethyl)-1,4,7-triazacyclononan-1-yl]acetamide (amino-dmptacn), for radioactivity-based detection. Transmission electron microscopic analysis and dynamic light scattering measurements confirmed the monodispersity and stability of the OPA-USPIONs in aqueous media and revealed a hydrodynamic size of ca. 15 nm. Furthermore, the biocompatibility and cellular uptake efficiency of the functionalised USPIONs was investigated in a range of normal and tumour cell lines. The results clearly show a cell type- as well as time-de