Molecular In Vivo Imaging Using a Noninvasive Cardiac-Specific MLC-2v Promoter Driven Dual-Gene Recombinant Lentivirus Monitoring System

Background Our study aimed to demonstrate the feasibility of using the sodium/iodide symporter (NIS) to monitor vascular endothelial growth factor (VEGF 165 ) expression in vivo. Methods We constructed a recombinant lentivirus plasmid with the MLC-2v promoter driving the sodium/iodide symporter (NIS) reporter gene linked to the VEGF 165 gene. Expression of NIS and VEGF gene were identified by Western blot. On days 2 and 54, 99m Tc-MIBI imaging was used to evaluate changes in myocardial ischemia. Noninvasive 125 I micro-SPECT/CT imaging was used to assess the expression of NIS reporter gene dynamically over the next 2 months. Results Western blot analysis showed that both NIS and VEGF 165 were highly expressed in rat cardiomyoblast H9C2 cells transduced with Lenti-MLC-2v-NIS--VEGF 165 . 125 I micro-SPECT/CT reporter imaging showed higher uptake in mouse myocardium transduced with Lenti-MLC-2v-VEGF 165 -IRES-NIS. NIS expression peaked on day 1 after transduction followed by a progressive decline to negligible levels by day 21. On day 1, mean 125 I activity value in group 1 was higher than that in group 2 ( P <0.05). The mean 125 I activity value in group 3 was statically lower than that in group 1 and 2 ( P <0.01). On day 60, 125 I uptakes in test and positive control groups became very low, and no significant differences in the mean 125 I activity values were detected between group 1 and group 2 ( P = 0.531 > 0.05). In group 1 (test group), 99m Tc-MIBI SPECT/CT revealed improvements in perfusion and wall thickening in the apical anterior wall. Mean IOD values of NIS and CD 34 were significantly higher in group 1 than group 3 ( P <0.05). Our study proved mean I-125 uptake was significantly correlated with mean IOD value of NIS and CD34 ( P <0.05). Conclusion This study demonstrates the feasibility of using the NIS gene to monitor VEGF 165 expression in a mouse myocardial ischemia model.