Radiolabeled, Antibody-Conjugated Manganese Oxide Nanoparticles for Tumor Vasculature Targeted Positron Emission Tomography and Magnetic Resonance Imaging.

Manganese oxide nanoparticles (Mn3O4 NPs) have attracted a great deal of attention in the field of biomedical imaging because of their ability to create an enhanced imaging signal in MRI as novel potent T1 contrast agents. In this study, we present tumor vasculature-targeted imaging in mice using Mn3O4 NPs through conjugation to the anti-CD105 antibody TRC105 and radionuclide copper-64 (64Cu, t1/2: 12.7 h). The Mn3O4 conjugated NPs, 64Cu-NOTA-Mn3O4@PEG-TRC105, exhibited sufficient stability in vitro and in vivo. Serial positron emission tomography (PET) and magnetic resonance imaging (MRI) studies evaluated the pharmacokinetics and demonstrated targeting of 64Cu-NOTA-Mn3O4@PEG-TRC105 to 4T1 murine breast tumors in vivo, compared to 64Cu-NOTA-Mn3O4@PEG. The specificity of 64Cu-NOTA-Mn3O4@PEG-TRC105 for the vascular marker CD105 was confirmed through in vivo, in vitro, and ex vivo experiments. Since Mn3O4 conjugated NPs exhibited desirable properties for T1 enhanced imaging and low toxicity, the tumor-specific Mn3O4 conjugated NPs reported in this study may serve as promising multifunctional nanoplatforms for precise cancer imaging and diagnosis.