title: Dynamic contrast-enhanced folate-receptor-targeted MR imaging using a Gd-loaded PEG-dendrimer-folate conjugate in a mouse xenograft tumor model.
abstract: OBJECTIVE
  The purpose of this study is to validate a folate-receptor (FR)-targeted dendrimer, PEG-G3-(Gd-DTPA)11-(folate)5, for its ability to detect FR-positive tumors, by using dynamic contrast-enhanced MRI.
  
  
  METHODS
  KB cells, FR siRNA knockdown KB cells, and FR negative HT-1080 cells, were incubated with fluorescein-labeled dendrimer and their cellular uptake was observed. Dynamic contrast-enhanced MRI was performed on mice-bearing KB and HT-1080 tumors and the enhancement patterns and parameters were analyzed.
  
  
  RESULTS
  Green fluorescence was found in the KB cells in the cellular uptake experiment, but was not seen in other settings. In the dynamic contrast-enhanced MRI, the 30-min washout percentage was -4 +/- 18% in the KB tumors and 39 +/- 23% in the HT-1080 tumors. A 17% cut-off point gave a sensitivity of 94.4% and a specificity of 93.8%.
  
  
  CONCLUSIONS
  We have demonstrated the targeting ability of PEG-G3-(Gd-DTPA)11-(folate)5 in vitro and in vivo. A 17% cut-off point for a 30-min washout percentage can be a useful parameter for the diagnosis of FR-positive tumors.
authors.affiliation: Department of Radiology, Taipei City Hospital, Taipei, Taiwan. wt2000.chen@msa.hinet.net
authors.forename: Wei-Tsung
authors.initials: WT
authors.lastname: Chen
authors.forename: Dhakshanamurthy
authors.initials: D
authors.lastname: Thirumalai
authors.forename: Tiffany Ting-Fang
authors.initials: TT
authors.lastname: Shih
authors.forename: Ran-Chou
authors.initials: RC
authors.lastname: Chen
authors.forename: Shin-Yang
authors.initials: SY
authors.lastname: Tu
authors.forename: Chin-I
authors.initials: CI
authors.lastname: Lin
authors.forename: Pang-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003287:Contrast Media; D050091:Dendrimers; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism; D019786:Gadolinium DTPA; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D023041:Xenograft Model Antitumor Assays
chemical_list: D002352:Carrier Proteins; D003287:Contrast Media; D050091:Dendrimers; D058973:Folate Receptors, GPI-Anchored; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D005492:Folic Acid; D019786:Gadolinium DTPA