Dynamic contrast-enhanced folate-receptor-targeted MR imaging using a gd-loaded peg-dendrimer-folate conjugate in a mouse xenograft tumor model

Purpose: 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. Procedures: 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. ? Academy of Molecular Imaging, 2009.