Dynamic contrast-enhanced folate-receptor-targeted MR imaging using a Gd-loaded PEG-dendrimer-folate conjugate in a mouse xenograft tumor model.
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.
Chen
Wei-Tsung
WT
Department of Radiology, Taipei City Hospital, Taipei, Taiwan. wt2000.chen@msa.hinet.net
Thirumalai
Dhakshanamurthy
D
Shih
Tiffany Ting-Fang
TT
Chen
Ran-Chou
RC
Tu
Shin-Yang
SY
Lin
Chin-I
CI
Yang
Pang-Chyr
PC
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
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