title: Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.
abstract: OBJECTIVE
  To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Long-Hua
authors.initials: LH
authors.lastname: Qiu
authors.forename: Jia-Wen
authors.initials: JW
authors.lastname: Zhang
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Li
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Yao
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Feng
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D000071063:Endoglin; D005682:Gadolinium / Q000008:administration & dosage; D005910:Glioma / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D000071063:Endoglin; C501740:Eng protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008081:Liposomes; D005682:Gadolinium
keywords: angiogenesis imaging; glioma; magnetic resonance imaging; tumor margins