VX2 Carcinoma In Rabbits With Self-made Ultrasmall Superparamagnetic Iron Oxide For MR: An Experimental Study

Part I MR imaging of VX2 carcinoma with self-made USPIO[Abstract] Objective The purpose of this study was to investigate the feasibility of tumor imaging with self-made Ultrasmall superparamagnetic iron oxide (USPIO) and the enhancement features of VX2 carcinoma in rabbits with USPIO bolus injection compared with gadopentetate dimeglumine, and then estimate the value of our contrast medium in tumor imaging.Methods USPIO was synthesized by single step in which Fe3O4 nanoparticles were packaged by dextran, and then the exosyndromes of the magnetic nanoparticles were evaluated. Seven rabbits inoculated VX2 carcinoma in both thighs, and six of them underwent conventional T1-weighted gadopentetate dimeglumine-enhanced magnetic resonance (MR) imaging and USPIO-enhanced T1-weighted,T2*-weighted MR imaging after two weeks of inoculation. The remained was used for control study in electron microscope and elemental analysis. The ROIs were respectively drawn in the tumor rim within the main tumor mass and muscular tissue nearby. Contrasto-to-noise ratio(CNR),percentage of enhancement and signal-to-noise ratio (SNR) were assessed. After MR imaging, Prussian blue staining,transmission electron microscope and elemental analysis were used to locate the USPIO and show the nanoparticles quantitatively.Results The composite USPIO exhibited satisfactory dispersibility and uniform shape which was always globular, and the diameter was 10 to 20 nm. Fourier transformation infared spectrometer(FTIR) demonstrated that the Fe3O4 nanoparticles packaged by dextran appeared some new absorption peaks(id est 3300cm-1,2925cm-1,1636cm-1,1427 cm-1,571cm-1), which indicated that the dextran had been coated successfully on the surface of magnetic nanoparticles. The tumors showed a steadily increasing contrast enhancement on T1-weighted USPIO-enhanced MR imaging, and significant signal loss in tumor at nonage on T2*-weighted USPIO-enhanced MRI. The CNR and percentage of enhancement all had statistical difference between different series (P<.01). Group comparison of postcontrast, CNR [were -8.40±3.00,1.84±1.39 and 4.11±1.55 respectively] also had significant difference between each series (P<0.0167), while the percentage of enhancement [were (-88.92±6.07)%,24.00% and (86.08±31.31)% respectively] didn't have statistical difference between gadopentetate dimeglumine- enhanced MRI and T2*-weighted USPIO-enhanced MRI (P>0.0167). The results of pathology,transmission electron microscope and elemental analysis all confirmed that the content of USPIO had notable difference between tumor and adjacent muscle; and in the tumor, the bulk of USPIO existed in tissue space and some of them even existed in the tumor cells.Conclusion VX2 carcinoma's vessel basal membrane had been shown to be microvascular hyperpermeable to USPIO. T2*-weighted USPIO-enhanced MR imaging can boost the enhancement effect of tumor, self-made USPIO had satisfactory features and can be phagocytized by tumor cells, which is a ideal contrast agent for tumor imaging. Part II MR evaluation of tumor angiogenesis in VX2 carcinoma with self-made USPIO[Abstract] Objective To evaluate the association of enhancement parameters at gadopentetate dimeglumine-enhanced magnetic resonance (MR) imaging versus Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced T1-weighted and T2*-weighted MR imaging with tumor angiogenesis in VX2 carcinoma in rabbits. To probe the value of MR imaging enhanced with macromolecular contrast media in quantitative characterization of tumor angiogenesis.Methods Six rabbits with experimentally induced VX2 carcinoma in both thighs underwent sequential MR imaging first with gadopentetate dimeglumine and then, 24 hours later, with USPIO. The ROIs were respectively drawn in the tumor rim within the main tumor mass and the tumor core. Maximum enhancement ratios(ERmax),Slopes and peak time (Tmax) were assessed; with regard to T2*-weighted USPIO-enhanced MR imaging, ERs of different time points (ER1 to ER6) were also selected for assessment. The Spearman correlation tests were used to determine the strength of the relationship between all the above parameters and microvessel density (MVD) and vascular endothelial growth factor (VEGF).Results We compared conventional T1-weighted gadopentetate dimeglumine -enhanced MRI to T1-weighted USPIO-enhanced MRI, and found that: The correlation coefficients which had notable statistical significance existed in the tumor rim on the whole; The highest correlation (r =0.87, P=.0002) was between the ERmax and VEGF in the tumor rim with USPIO, the correlation coefficients were lower with injection of gadopentetate dimeglumine than those with USPIO. The signal decrease (SD) of tumor showed a dependent effect, but no linear relationship with microvascular density at T2*-weighted USPIO-enhanced MRI. The correlation coefficients between enhancement parameters and pathologic parameters at T2*-weighted USPIO-enhanced MRI were close to T1-weighted imaging, but different from the latter, it was a negative correlation. The highest correlation was between the ER2 and pathologic parameters, which were -0.82 (P<.01) and -0.76 (P<.02) respectively, followed by correlation coefficients descending gradually, until ER6 and ERmax no correlation had been shown.Conclusion USPIO-enhanced T1-weighted and T2*-weighted MR imaging have parallel potential in estimating tumor angiogenesis by enhancement parameters. Blood pool contrast media USPIO permits more accurate evaluation of tumor angiogenesis compared with gadopentetate dimeglumine.