Application of NRP-1 targeting molecular probe in grading diagnosis of heterotopic brain glioma in nude mice / 中华行为医学与脑科学杂志

ABSTRACT

Objective To observe the expression of neuropilin-1 (NRP-1) in glioma cells of different grades,and evaluate the application value of a novel molecular probe(USPIO-PEG-tLyP-1)in the grading diagnosis of heterotopic glioma in nude mice by magnetic resonance imaging (MRI).Methods Expression levels of NRP-1 in glioma cell lines of different grades were detected by Western-Blot.USPIO-PEG-tLyP-1 was synthesized by carbon diimine method.The U87-MG tumor-bearing mice model (U87-MG group) and CHG-5 tumor-bearing mice model(CHG-5 group) were established with 10 mice in each group.Six tumorbearing mice with a tumor volume about 0.6 cm3 were selected from each group,and they were given with 2mg/kg molecular probes via tail vein respectively and was detected by MRI at 0 h,6 h,12 h and 24 h,then R2 values were calculated.After the imaging,tumor-bearing mice were sacrificed,and tumor tissue sections were made.The iron particles in the sections was detected by Prussian blue staining.The binding ability of molecular probes and tumor tissues in the two groups was compared.Results The expression of NRP-1 in U87-MG and CHG-5 cell lines was significantly higher than that in HA.In addition,the expression of NRP-1 in U87-MG was higher than that in CHG-5 cell(P＜0.01).MRI results showed that R2 values of tumor tissues in the two groups were compared,and the difference was not statistically significant before the injection of molecular probe(U87-MG group(10.35±0.52)vs CHG-5 group(9.86±0.43),t=1.779,P=0.106).The R2 value of tumor tissue in the U87-MG group was higher than that in the CHG-5 group after the injection of molecular probe (6 hU87-MG group (11.63±0.85)vs CHG-5 group (10.51 ±0.49),t=2.796,P=0.019;12hU87-MG group(14.23±0.68)vs CHG-5 group(12.29±0.28),t=6.462,P=0.000;24 hU87-MG group (13.36±0.92) vs CHG-5 group(11.32±0.64),t=4.459,P=0.001).The results of Prussian blue staining showed that there were significantly more blue staining particles in tumor tissues of the U87-MG group than that of the CHG-5 group,and the difference was statistically significant(P＜0.01).Conclusion The NRP-1 targeted molecular probe can be used for grading diagnosis of high and low grade heterotopic brain glioma in nude mice.