The In Vivo Study Of Peptid Based Molecular Probe For CXCR4Imaging In Pancreatic Cancer Xenograft Model

Objective:To investigate the biodistribution of Pep12-USPIO and USPIO in BALB/c nude mice. To evaluate the targeted imaging capability of Pepl2-USPIO in human pancreatic cancer xenograft nude mice model.Method:Human pancreatic cancer cell line BxPC-3, PANC-1was incubated with Pep12-USPIO and USPIO respectively in serum containing culture medium. Prussian blue staining of the iron particles and in vitro magnetic resonance scanning was performed. Different doses of Pepl2-USPIO, USPIO were injected through tail vein of nude mice, MRI scanning was performed on different time points. T2values of different organs was measured at each time point. Organs of the mice was harvested for Prussia blue iron staining on24h or48h post injection. Human pancreatic cancer xenograft model was established with BxPC-3or PANC-1cell lines; different dose of Pep12-USPIO was injected via the tail vein of nude mice. MRI scanning was performed at each time point to measure the T2value of tumor region. Tumor tissue was collected for Prussia blue iron staining on24h or48h post injection. Immunohistochemistry test for CXCR4expression of the tumor was performed.Results:In vitro study confirmed the targeted imaging capability of Pep12-USPIO in human pancreatic cancer. Prussian blue iron stain showed iron particles were mainly distributed in the liver, spleen, lymph node. No obvious iron particle observed in kidney, brain, muscle, heart and lung. When USPIO dose reached1000μ mol Fe/Kg, small amount of iron particles was found in kidney and muscle. The effect of Pep12-USPIO on tumor region T2value showed no significant difference when compared with USPIO (P>0.05). No iron particle distribution was found in tumor tissue. Tumor CXCR4immunohistochemistry showed no or weak expression of CXCR4.Conclusion:After administration via tail vein, Pep12-USPIO and USPIO is mainly distributed in the liver, spleen, lymph node. No significant distribution was observed in kidney, muscle, heart, lung, and brain tissue. The effect of targeted imaging of Pep12-USPIO was not observed in human pancreatic cancer xenograft model. tumor tissue from the xenograft model show no or low expression of CXCR4.