Study of glioblastoma multiforme metastatic and invasive mechanism by polycistronic imaging probe in tumor implanted animal model

[[abstract]]Objectives Glioblastoma Multiforme patients suffering from malignant brain tumors were mostly informed that the mean survival lifespan is about a year after diagnosis. Metastasis of glioblastoma is often defined for the invasiveness of lesion from one side of the brain to the other, instead of relocation somewhere distant from the original site. In animal models, fluorescent proteins were extensively applied in tumor labeling; however, orthotopic brain tumors are located inside skulls that fluorescent signals are unable to penetrate through. Several multi-modality imaging study with different strategies had been done to link those reporter genes, such as internal ribosomal entry site (IRES) linking and fusion proteins. Recently, a multicistronic linker named 2A peptide were identified and applied on polycistronic gene expression construct. Methods We built up several multi-modality imaging probe by 2A-peptide linkers. These lentiviral-based constructs were capable for fluorescent, bioluminescent, and nuclear medicine imagine. Tumor response was evaluated via suicidal gene therapy and immunotherapeutic gene thearpy. Results We demonstrated the multi-modality imaging in orthotopic tumor-bearing mice model. The tumor response under imaging surveillance were compatible to the caliper measurement and post-mortem analysis. Conclusions Compare to fusion proteins and IRES-linked reporters, our results displayed the stable and even expression in cell and animal model. Thus, we performed this multicistronic reporter system is able to provide modality-on-demand imaging service