Experimental Design

In the current study, we used synthetic polymeric vectors based on pseudodendritic oligoamines with high intrinsic tumor affinity (G2-HD-OEI) to target a NIS-expressing plasmid (CMV-NIS-pcDNA3) to neuroblastoma (Neuro2A) cells.

Results

Incubation with NIS-containing polyplexes (G2-HD-OEI/NIS) resulted in a 51-fold increase in perchlorate-sensitive iodide uptake activity in Neuro2A cells in vitro. Through 123I-scintigraphy and ex vivo gamma counting Neuro2A tumors in syngeneic A/J mice were shown to accumulate 8% to 13% ID/g 123I with a biological half-life of 13 hours, resulting in a tumor-absorbed dose of 247 mGy/MBq 131I after i.v. application of G2-HD-OEI/NIS. Nontarget organs, including liver, lung, kidneys, and spleen revealed no significant iodide uptake. Moreover, two cycles of systemic NIS gene transfer followed by 131I application (55.5 MBq) resulted in a significant delay in tumor growth associated with markedly improved survival.

Conclusions

In conclusion, our data clearly show the high potential of novel pseudo-endritic polymers for tumor-specific NIS gene delivery after systemic application, opening the prospect of targeted NIS-mediated radionuclide therapy of nonthyroidal tumors even in metastatic disease.