title: Targeting an ultrasound contrast agent to folate receptors on ovarian cancer cells: feasibility research for ultrasonic molecular imaging of tumor cells.
abstract: OBJECTIVE
  The purpose of the study was to synthesize and characterize folate-targeted microbubbles (MB(F)) as an ultrasound contrast agent and to evaluate their affinity to the folate receptor (FR) in vitro.
  
  
  METHODS
  Folate-targeted microbubbles were prepared by incorporating 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000]-folate into the lipid membrane of microbubbles. The diameter and concentration of the MB(F) were determined by a cell counter and sizer. The MB(F), control microbubbles (MB(C)), and MB(F) with a free folic acid block-ade were tested for binding specificity to human ovarian carcinoma SKOV3 cells, which overexpress the FR, by microscopy and confocal imaging, respectively.
  
  
  RESULTS
  The basic physical characteristics of MB(F) were similar to those of MB(C). In the cell binding test, the adherence efficiency of MB(F) to the SKOV3 cells (mean +/- SD, 16 +/- 5 microbubbles per cell; P < .01) was significantly higher than that of MB(C) (0.7 +/- 0.4 microbubbles per cell) or MB(F) with the free folic acid blockade (0.7 +/- 0.6 microbubbles per cell).
  
  
  CONCLUSIONS
  Folate-targeted microbubbles showed high affinity to SKOV3 cells with FR overexpression. They are potentially useful for ultrasonic molecular imaging and treatment of FR-positive tumors and warrant further investigation.
authors.affiliation: Department of Ultrasound in Medicine, Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Xing
authors.forename: Wang
authors.initials: W
authors.lastname: Zhigang
authors.forename: Hu
authors.initials: H
authors.lastname: Bing
authors.forename: Ran
authors.initials: R
authors.lastname: Haitao
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Xu
authors.initials: X
authors.lastname: Chuanshan
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yuanyi
authors.forename: Li
authors.initials: L
authors.lastname: Ao
mesh_terms: D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D005026:Ethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D045423:Microbubbles; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging*; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured; D014463:Ultrasonography
chemical_list: C509678:1,2-distearoyl-sn-glycero-3-phosphatoethanolamine-N-(amino(poly(ethylene glycol))); D003287:Contrast Media; D005026:Ethylene Glycols; D011956:Receptors, Cell Surface; D005492:Folic Acid; D005990:Glycerol