Molecular imaging enables the non-invasive 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 study, spontaneously forming, small unilamellar vesicles (sULVs)
(30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic
resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain
tumors. sULVs 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 sULVs were
characterized in vitro using small angle neutron scattering (SANS), phantom MRI and
dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded
sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice
using time domain optical imaging and MRI. The results demonstrated that a
spontaneously forming, nanosized ULVs loaded with a high payload of Gd can
selectively target and image, using MR and optical imaging, brain tumor vessels when
functionalized with anti-IGFBP7 single domain antibodies. The unique features
of these targeted sULVs make them promising molecular MRI contrast agents.