ABSTRACT
Objective To investigate the potential of AFP-targeted ultrasmall superparamagnetic particles of iron oxide (USPIO) molecular probe in specific detection of hepatocellular carcinoma (HCC) with MRI.Methods The targeted probe was synthesized by conjugating AFP antibody with modified USPIO.Two groups treated with AFP-USPIO and USPIO were set up in the study.The HepG2 cells were incubated with AFP-USPIO or USPIO (100 μg/ml) respectively with the dosage of 50 μ1,100 μl or 150 μl for 4 hours,followed by MR imaging in vitro.The signal-noise ratio (SNR) of the cells on T2-weighted image (T2WI) was measured.The rat models with orthotopic HCC were divided into two groups with 5 rats for each group at random.Pre-and post-contrast enhanced (after 1 hour) MR imaging were performed with caudal vein injection at a dosage of 20μg/ml.The contrast noise ratio (CNR) on T2WI and the difference of CNR between pre-and post-enhancement or between both groups were calculated.The relationship of SNR or CNR with the iron particles in cells or tumors was confirmed by Prussian blue iron staining.Results Cytology experiment showed the SNR in both groups was decreased with the increase of the dosage of AFP-USPIO or USPIO,indicating statistically significantdifference in SNR among three different doseage groups (P＜0.05).Prussian blue iron staining showed that the iron particles in cells were increased with the increase of AFP-USPIO dosage,and was negatively correlated with SNR (P=0.00,r=-0.926).However,the iron particles were less in cells in USPIO group.The CNRs of liver tumors in Wistar rat of pre-and post-AFP-USPIO injection were 2.05±0.88 and 0.96±0.31 respectively,indicating a significant difference (P=0.028,t=3.380).However,the CNRs in USPIO group,2.25±1.50 and 2.57±1.49,showed no statistical difference (P=0.275,t=1.263).The CNR after enhancement also had a statistical difference between both groups(P=0.042,t=3.487).Pathological results confirmed more iron particles in tumor tissues in AFP-USPIO group,whereas less in USPIO group.Conclusion AFP-USPIO molecular probes can initiatively target to the HepG2 cells and the liver cancer of rat models expressing AFP,which may help to achieve the specificity of MR imaging in the diagnosis of HCC.
ABSTRACT
Objective To observe signal changes induced by USPIO accords with iron swallowed by macrophages in brain tissue sections in rats. Methods Thirty-eight SD rats were divided into two groups randomly. Three of them were involved in sham operation group, other thirty-five rats were divided into five subgroups averagely according to 7.0T MR scanning time (6 h, 12 h, 24 h, 48 h and 72 h). After establishment of MCAO models, USPIO was injected to tail intravenous and monitored with high resolution MRI at different time point, while rats in control group were injected with the same dose of sodium chloride. Brain tissue wax section was acquired after MR scanning. Cell necrosis, iron particle and activated macrophages were observed with HE dying, Prussian Blue dying and CD68 immunochemistry staining respectively. Results The ischemic lesion was detected as hyperintense area on T2WI after occlusion and perfusion of MCA. The accumulation of USPIO appeared as hypointense on T2WI but hyperintense on T1WI. The maximum signal change was observed at 48-72 h in both T1WI and T2WI (P>0.05). The iron particle accumulation was found in the boundary of ischemic lesion and necrotic area with Prussian Blue dying. Activated microglia was manifested with CD68 immunochemistry staining, the number of microglia at 72 h was more than those of the other time points. Conclusion USPIO can be used as a contrast agent to monitor rat ischemic stroke in vivo, and the signal changes induced by USPIO approximately accord with iron swallowed by macrophages in brain tissue sections. The cells which swallow USPIO are mainly activated macrophages.