Study On The Changes Of Signal Intensity And MRI Imaging Of Tumor Tissue In Nude Mice-bearing Tumor Using SPIO-shRNA Molecular Probe

PART1SPIO-SHRNA MOLECULAR PROBE INJECTION TO EXPLORE MR-BASED SIGNAL CHANGES AT DIFFERENT TIME POINTS AND OPTIMAL SCANNING TIME IN TUMOR-BEARING NUDE MICEObjective:To investigate the molecular probe SPIO-shRNA tumor-bearing nude mice in vivo tumor regional signal changes,clarify the optimal scanning time of molecular probe in vivo MR imaging.Methods:30 BALB/c tumor-bearing nude mice were randomly divided into six groups.Each group was performed Magnetic Resonance scans before and after injection of SPIO-shRNA molecular probe at different timing（12h,24h,27h,30h,36h）with a Iron concentration of18mg·kg^-1,followed by a sacrifice after the above test.Tumor and adjacent muscle tissue were obtained for HE and Prussian Blue staining and further observation under light microscope.In addition,the signal intensity in both tumor and adjacent muscle tissue was measured at different points in time.Results:Notable difference of tumor signal intensity was detected at27h after injection of molecular probe.The signal in T2WI sequence reached peak at the 27h showing a statistical significance（P<0.05）than the any other point-in-time.In addition,signal intense in T2WI sequence hit the bottom at the 27h as well as T2*GRE sequence,and this difference is significant（P<0.001）HE staining indicated disorganation in tumor tissue as well as increasement of atypia.Prussian Blue staining showed that iron particles were distributed dispersedly at different timing points but the most abundant expression is at 27h.Conclusion:Tumor tissue could be well labeled with SPIO-shRNA molecular probes,and the optimal MR scanning time is at 27h after injection.PART2 OPTIMAL SCANNING CONCENTRATION OF MR IMAGING FOR TUMOR-BEARING NUDE MICE WITH SPIO-SHRNA MOLECULAR PROBEObjective: To investigate MRI signal variation and the optimal scanning concentration for tumor-bearing nude mice with SPIO-sh RNA molecular probes.Methods: 30 BALB/c tumor-bearing nude mice were randomly divided into five groups（6 mice in each group）.Iron content were administrated respectively through tail vein injection with 6mg·kg^-1,12mg·kg^-1,18mg·kg^-1,24mg·kg^-1,30mg·kg^-1,simultaneously performing MR examination to measure signal intensity in tumor tissue and contralateral muscle tissue.After treatments above,the nude mice were sacrificed,and tumor and muscle tissues were sampled for HE and prussian blue stain.Results: Groups(6mg·kg^-1,12mg·kg^-1,18mg·kg^-1)were all survived after probe injection,but the nude mice were partly dead in 24mg·kg^-1 and30mg·kg^-1 groups after injection or during scanning process.The most marked signal changes were T2 WI and T2*GRE;the signal intensity of the tumor tissue in 18mg·kg^-1,24mg·kg^-1 and 30mg·kg^-1 groups were most obvious（P〈0.05）,while the 18mg·kg^-1,24mg·kg^-1 and 30mg·kg^-1 groups reached no statistical difference（P 〉 0.05）;HE staining indicated disorganation in tumor tissue as well as increasement of atypia.Prussian Blue staining showed that iron particles were distributed dispersedly in each experimental group,and the most abundant expressions were in18mg·kg^-1、24mg·kg^-1、30mg·kg^-1 groups.Conclusion:Tumor tissue could be well labeled with SPIO-shRNA molecular probes,and the optimal MR scanning concentration is 18mg·kg^-1.