pH-sensitive methionine-decorated magnetite for targeted MRI/SPECT cancer imaging

Chelator-free radiolabeling of nanoparticles (NPs) has attracted a great interest in design of targeted contrast agents for multimodal imaging. Herein, we present a new dual-modality contrast agent based on the efficient radiolabeling of Fe₃O₄ magnetic nanoparticles (MNPs) with ^99mTc for targeted MRI-SPECT cancer imaging. Methionine (Met) was conjugated to maleic anhydride-alt-1-octadecene (PMAO) and employed as a coating agent, endowing Fe₃O₄ MNPs with appropriate colloidal stability, biocompatibility, binding affinity to ^99mTc, and targeting ability. The morphology, size, surface charge, crystallinity and functionality of the targeted contrast agent (Fe₃O₄@PMAO-Met) were fully characterized. The MTT assay confirmed high biocompatibility of Fe₃O₄@PMAO-Met MNPs (∼35 nm) in MCF-10A normal mammary epithelial cells, and enhanced uptake in MCF-7 breast cancer cells, supporting their targeting capability. The ^99mTc-labeled MNPs with reproducible high yield (>98 %) at room temperature remained permanent in vitro for 24 h in saline and for 6 h in human serum. Fe₃O₄@PMAO-Met MNPs was also evaluated in vivo in mice models, exhibiting acceptable tumor visualization as well as noticeable hepatobiliary uptake with low accumulation in non-target organs. In vivo MR imaging of Balb/c mice revealed a negative T₂ enhanced contrast on tumor cells. All assessments demonstrated high potential of Fe₃O₄@PMAO-Met-^99mTc for further analyses as a promising targeted contrast agent in MRI-SPECT cancer imaging.