Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.

Purpose: To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model.

Materials And Methods: Four liposome preparations, including nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio-MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step pretargeting imaging, were formulated. All animal experiments were carried out with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR. T1 -weighted MRI was performed before and dynamically repeated after different contrast agents were injected. The enhancement features of the tumors were compared.

Results: The signal enhancement of the tumor in the two-step pretargeting group increased by 117.9 ± 5.3% at the periphery and 109.2 ± 3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs injection. Ring-like enhancement margins were demonstrated at the periphery of the tumor in the two-step targeted group. The specificity of the targeted liposomes was supported by the competitive study. The signal of peak enhancement using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly higher than the non-targeted groups.

Conclusion: The two-step endoglin-targeted imaging using biotin-streptavidin interaction was demonstrated to induce intense enhancement of the tumor periphery, which implies that this advanced MR molecular contrast agent may be suitable for accurately delineating glioma tumor margins. J. Magn. Reson. Imaging 2015;41:1056-1064. © 2014 Wiley Periodicals, Inc.