Targeted MRI and optical molecular imaging using gadolinium loaded small unilamellar vesicles

Noninvasive investigation of cellular and molecular processes becomes possible through the novel techniques, one of which is molecular imaging, where enhanced sensitivity is a key component for clinic translation of the technique. In this presentation, spontaneously forming, small unilamellar vesicles (ULVs) (30 nm 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 mice brain tumor model 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.