| Objective: To explore the value of magnetic resonance molecular probe USPIO-PEG-sLeX which was consisted of sLeX and Ultrasmall Superparamagnetic Iron Oxidem(USPIO)in a nude mouse model of nasopharyngeal carcinoma(NPC).The difference of T2* value caused by the binding of USPIO-PEG-sLeX in the metastatic group and the non-metastasis group was measured.The expression of E-selectin in nude mice was inhibited by cimetidine,and molecular imaging was again used to detect molecular probes.Targeting effect on the body E-seletcin.Methods: The nasopharyngeal carcinoma(NPC)cell 5-8F was cultured.A total of 12 Balb/c female nude mice were modeled on the left paw pad.Routine anesthesia was performed 8 weeks after inoculation.Magnetic resonance T2*mapping was performed before and after USPIO-PEG-sLeX injection 0h,1h,2h,and the time points before and after injection were compared.T2* value,T2*difference(?T2* value),and enhancement rate(ER)at each time after enhancement.After the scan was completed,the nude mice were sacrificed and detailed anatomical examination was performed to observe the tumor and thepresence or absence of metastasis.The specimens of transplanted tumors and suspicious metastatic nodules were embedded in formalin and sectioned.Metastasis was performed and immunohistochemical staining was used to analyze the expression of E-selectin in transplanted tumors.Another 24 nude mice were subcutaneously cast,and the expression of E-selectin was inhibited by cimetidine injection.Magnetic resonance T2*mapping was performed 8 weeks after modeling to analyze the change of T2*value before and after molecular probe injection.The ability of the molecular probe USPIO-PEG-sLeX to target E-selectin was verified.Results: Compared with the non-metastatic group of nude mice E-selectin,the mean optical density(MOD)of the metastatic group was significantly higher than that of the non-metastatic group(0.52±0.24 VS 0.08±0.01,P<0.05).There was no significant difference in the plain T2* values between the two groups of nude mice(22.25±8.08 vs 27.01±9.45,P>0.05).At the three time points of 0h,1h and 2h after the injection of molecular probes in the tail vein of the two groups,the T2* values of the metastatic group were lower than those of the non-metastasis group,and the values were 11.57±4.02 VS24.82±7.84,10.09±4.88 VS.24.15±8.74,12.46±5.63 VS 23.42±7.12,P valueswere less than 0.05,the difference was statistically significant.The T2*values of the two groups at 0h,1h and 2h after the injection of molecular probes in the tail vein of the two groups were higher than those in the non-metastasis group,which were 10.69±6.23 VS 3.86±2.20,12.17.±8.67 VS2.87±1.37,9.80±3.03 VS 4.32±2.28,P values were all less than 0.05,the difference was statistically significant.At 0h,1h and 2h after injection of molecular probes in the tail vein of the two groups,the ER in the metastatic group was higher than that in the non-metastasis group,and the values were45.98±14.03 VS 7.10±5.18,51.15±22.70 VS 11.04±6.01,44.05±13.92,respectively.VS 12.09 ± 7.54,P values were less than 0.05,the difference was statistically significant.After cimetidine inhibited the expression of E-selectin,the expression of E-selectin in subcutaneous xenograft model of nude mice was lower than that of normal saline control group(0.040±0.009 VS 0.6805±0.008,P<0.05).It is statistically significant.There was no significant difference in the plain T2*values between the two groups of nude mice(22.40±7.61 VS 29.54±9.52,P>0.05).MRI scan was performed at 0h,1h,and 2h after molecular injection of USPIO-PEG-sLeX in the tail vein.There was no significant difference in T2*between the two groups at each time point(16.59±5.38 VS 16.81±6.08,13.44±4.57).VS 12.27 ± 3.49,12.30 ± 3.69 VS 12.18 ± 3.98),P values are > 0.05.There were significant differences in ?T2* values between the two groups of nude mice at 0h,1h,and 2h(6.08±5.65 VS 13.04±9.83,8.96±6.54 VS 17.28±9.52,10.11±6.07 VS 17.37±9.57).P values were all<0.05.The ER difference between the two groups of nude mice at 0h and 1h after injection of contrast agent was statistically significant(21.23±14.68 VS40.79±20.05,36.39±20.26 VS 55.37±15.54),P value was less than 0.05.There was no significant difference in ER between the two groups of mice at 2 h after injection of contrast agent(42.12±16.14 VS 55.69±16.08,P>0.05).Conclusions: E-selectin is highly expressed in NPC xenografts and is closely related to the metastasis of nasopharyngeal carcinoma.It is an important molecular marker for metastasis of nasopharyngeal carcinoma and can be used as a molecular probe target.The molecular probe USPIO-PEG-sLeX can be successfully targeted to the transplanted tumor E-selectin,which is expected to be a specific MRI molecular probe for NPC.It can be used for early diagnosis ofNPC,early detection of metastases,and dynamic monitoring and evaluation of E-selectin.Changes can provide a basis for clinical development of NPC treatment and precision treatment. |
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