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, t_1/2: 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.