Expression of the sodium-iodide-symporter (NIS) in neuroendocrine tumors (NET) using the chromogranin A promoter in adenoviral vectors

Neuroendocrine tumors (NET) are neoplasm of the gastroenteropancreatic system (GEP), originating from the interface between the endocrine and the nervous system.

NET-tumors are often malignant, and the medical treatment is not successful at present. Therefore new and more effective experimental therapies are emerging.

Thyroid cancer can be efficiently treated by the application of radioactive Iod¹³¹, because of the sodium-iodide-symporter (NIS), which is expressed in thyroid cells only.

Chromogranin A (CgA) is produced in 80–100% of NET cells and serves as a biochemical marker. This overexpression is caused by the high activity of the CgA promoter.

In order to obtain a neuroendocrine-dependent expression of NIS we developed non-replicative adenoviral vectors, which either expressed NIS under the control of the strong viral Cytomegalovirus (CMV) promoter (as possitive control) or the tissue-specific CgA promoter respectively. To prove the adenovirus-mediated NIS expression in NET cells radioactive Uptakes with Iod¹²⁵, ^99mTc and Iod¹³¹ were performed.

It can be concluded that CgA promoter targeted NIS-expressing neuroendocrine tumor cells, efficiently concentrate radioisotopes inducing cytotoxicity.

The results of this study shown the potential of tumor-specific NIS gene transfer which could be an innovative strategy for radioiodide based treatment of neuroendocrine tumors.