Targeted MRI and Optical Molecular Imaging Using Gadolinium Loaded Small Unilamellar Vesicles

Molecular imaging enables the noninvasive investigation of cellular and molecular processes.  Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this presentation, spontaneously forming, small unilamellar vesicles (ULVs) (30nm in diameter) were used as a platform to build a bi-modal [i.e., optical and Magnetic Resonance Imaging (MRI)] targeted contrast agent for the molecular imaging of brain tumors.  Small ULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant ULVs were characterized in vitro using small angle neutron scattering (SANS), in phantom MRI and dynamic light scattering (DLS). Targeted (with antibodies) and nontargeted-Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using both optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULV loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with antibodies. The unique features of these targeting ULVs make them promising molecular MRI contrast agents.