Studies with hNIS cDNA transfected human glioma cells also showed increased cytotoxicity of 131I if cells were grouped in a three-dimensional spheroid culture compared to a monolayer culture. This was believed to be due to bystander toxicity, which is maximized in a three-dimensional model. As a corollary, to maximize the therapeutic effect of hNIS, high level transduction and expression are required. Thus, aiming for high level expression of hNIS makes sense not only for maximal radioisotope uptake but also to ensure adequate retention if the isotope is to have its desired effect. In our study, little 188Re is retained in the thyroid gland, as 188Re cannot be organified by this organ. Studies have demonstrated a similar biodistribution pattern for 131I and 188Re in mice, with the exception of the thyroid gland, in which only 131I is retained by organification. In fact, the absence of organification of 188Re by the thyroid gland may also be considered an advantage for therapy of nonthyroidal hNIS-bearing tissues, in that the thyroid will not serve as a sink for radiopharmaceuticals and will sustain less radiation damage, and more 188Re can be uptaken by U87-hNIS cells due to 188Re recirculation. TCS OX2 29 Considering that in our current study a stably hNIS transfected cell line was used with maximum hNIS expression levels, which is not directly applicable for clinical use in humans, the efficacy of 188Re needs to be evaluated further in future studies after systemic in vivo hNIS gene transfer with the typical limited transduction efficiency and a more heterogeneous hNIS expression pattern. Provided that these studies confirm our findings, 188Re may serve as an attractive alternative to 131I, particular in tumors with short iodide retention time. Due to aggressive growth and a high metastatic rate during the early stage, pancreatic cancer remains a highly lethal malignant disease, and only approximately 10�C20% of pancreatic cancer is resectable at the time of SKF 77434 hydrobromide diagnosis. Gemcitabine has been the standard treatment for advanced pancreatic cancer; however, the median survival is 5�C6 months, with the frequent development of chemo-resistance during the treatment. Thus, pancreatic cancer remains a dreadful disease, and there is an urgent need of further studies to reveal the molecular mechanisms of tumor invasion and metastasis to develop an effective therapeutic approach to prevent and/or treat of pancreatic cancer. Cancer associated fibroblasts, predominant components of the tumor stroma, have been extracted from several invasive human carcinomas, including pancreatic cancer.