Primary Study Of Specific Targeting Of Tumor Angiogenesis By RGD-Conjugated GoldMag^TM-CS Nanoparticles With A Clinical 3.0T Magnetic Resonance Scanner

Objective To prospectively evaluate the ability of cyclic arginine-glycine -aspartic- D-phenylalanine-lysine -conjugated- GoldMagTM-CS nanoparticles to depict tumor angiogenesis with a clinical 3T MR scanner system in vitro and in vivo.Methods Construction of MR Specific molecular probes used GoldMagTM-CS nanoparticles and c(RGDfK) by noncovalent bond couple. The expression of integrinα_vβ₃ in cultured ECV304 cells was determined using a serial of methods including immunohistochemistry, flow cytometry, immunofluorescence, etc. The capability of synthesized probes specially targeted to ECV304 cells was proved by observation of flow cytometry. MR scan sequences were established and the RGD@GOLDMag solution in different concentration was scanned to ascertain the lowest concentration that can be detected by MR system. The ability of RGD@GOLDMag to noninvasivesily image tumor angiogenesis was evaluated using a clinical 3.0 T MR scanner in vitro(ECV304) and in vivo(nude mice beared HepG2 hepatic cancer). 15 tumor-bearing mice were averagely randomly divided into three groups: A, RGD@GOLDMag group; B,NRGD@GOLDMag group; and C, competitive group. T2* weighted MRI which was used to spatially and temporally determined nanoparticles deposition in the tumor were generated before and 0.5h,1 h after the contrast agent was injected. The tumors were dissected for Correlative histologic analysis (including hematoxylin-eosin (HE) staining, immunohistochemical (IHC) staining) after the last MR scan.Unpaired student t test and Spearman nonparametric correlation coefficient were used for statistic analysis.Results RGD@GOLDMag was successfully constructed , which could specifically target ECV304 cells and obviously decrease the MRI signal intensity(SI). The SI significantly decreased in the tumor of A group compared with that of B and C group (p<0.05). Tumor histologic analysis confirmed the extent and asymmetric distribution of neovascularity observed by MRI. Conclusions RGD@GOLDMag has the potential to specifically detect and characterize solid tumor angiogenesis with a clinical 3.0 Tesla MR scanner.