title: Imaging of brain tumors with paramagnetic vesicles targeted to phosphatidylserine.
abstract: OBJECTIVE
  To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors.
  
  
  METHODS
  Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain.
  
  
  RESULTS
  The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)(-1) relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%).
  
  
  CONCLUSIONS
  These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS.
authors.affiliation: Department of Radiology, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Winter
authors.forename: John
authors.initials: J
authors.lastname: Pearce
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Chu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: McPherson
authors.forename: Ray
authors.initials: R
authors.lastname: Takigiku
authors.forename: Jing-Huei
authors.initials: JH
authors.lastname: Lee
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Qi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D010713:Phosphatidylcholines / Q000493:pharmacokinetics; D010718:Phosphatidylserines / Q000378:metabolism*; D014018:Tissue Distribution; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: C462319:1-strearoyl-2-arachidonyl-sn-glycero-3-phosphatidylcholine; D014408:Biomarkers, Tumor; D003287:Contrast Media; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D053835:Unilamellar Liposomes; D019786:Gadolinium DTPA
keywords: MRI; cancer; contrast agent; glioblastoma multiforme