In vivo Radioiodide Imaging and Treatment of Pancreatic Cancer Xenografts after MUC1 Promoter-Driven Expression of the Human Sodium-Iodide Symporter

The Biology of the Sodium Iodide Symporter and its Potential for Targeted Gene Delivery

“…It has been shown previously that the effective biological half-life of 131 I in these circumstances ranges from approximately 5-10 hours [147,151,152], which is far less than that observed within the normal thyroid gland.…”

“…Additional use of targeted radiosensitising drugs can lead to further synergistic interactions between radioisotopic irradiation and EBRT. [148] in vitro and in vivo pancreatic cancer functional and therapeutic Adenoviral vector expressing hNIS regulated by MUC1 promoter (Ad-MUC1-NIS) 43-fold increase in iodide uptake in vivo scintigraphy − 13% of injected iodide retained by tumours -optimal uptake at 5 hrs in vivo therapeutic effect with 131 I (>50% reduction in tumour volume) (p<0.0001) Dwyer (2007) [149] in vitro and in vivo ovarian cancer functional and therapeutic [151] in vivo medullary thyroid cancer functional and therapeutic AV vector expressing hNIS regulated by CEA promoter (Ad-CEA-NIS) IT injection -5 × 10 8 PFU iodide retention of 7.5 +/− 1.2% ID/g biological half-life − 6.1 ±0.8hrs significant reduction in tumour growth with 131 I with reduction in calcitonin levels Willhauck (2007) [152] in vitro and in vivo hepatocellular carcinoma functional and therapeutic stably NIS-tranfected murine hepa-1-6 and human hepG2 cell lines > 75% cell-death following exposure to 131 I hepG2 xenografts accumulated 15% of 123 I biological half-life of 8.4 hours tumour-growth inhibition after 55MBq of 131 I Dwyer (2005) [153] in vivo adult male beagle dogs safety and feasibility study Adenoviral vector expressing hNIS regulated by CMV promoter (Ad-CMV-NIS) 123 I scintigraphy using SPECT/CT average-absorbed dose of 23 ±42 cGy after 1 mCi 131 I average-absorbed dose of 1245.1 ±280.9 cGy…”

“…The average tumour activities per gram at 1, 3, 5 and 7 hrs were 10.8, 12, 9.9 and 7%, respectively, and had decreased to 3% by the 24 hour time point with an effective biological half-life of 10.5 hrs. Following a therapeutic dose of 131 131 I resulted in a significant reduction of tumour growth associated with significantly lower calcitonin serum levels in treated mice as well as improved survival [151]. More recently, the same group has published on another study in which NIS expression was driven by the tumour specific promoter (alfa-fetoprotein (AFP)) in a hepatocellular carcinoma model.…”

“…Furthermore, this correlated with a reduced level of NIS protein expression on western blot analysis [134]. Most subsequent studies have employed low-iodine diets combined with T4 supplementation (0.05-5 mg/l) for 1-2 weeks prior to radioiodide therapy [128,[150][151][152][153]. The effectiveness and feasibility of using this protocol can be gauged from the study by Wapnir et al (2004) that was performed in patients with metastatic breast cancer [109].…”

“…Most commonly, NIS gene expression has been mapped using pertechnetate ( 99m TcO 4 − )-or iodide ( 123 I)-based scintigraphic techniques with conventional gamma camera imaging [138,[150][151][152] or SPECT/CT [153]. Scintigraphic assessment enables estimation of the level of radioisotope uptake and the effective half-life within the NIS-transduced tumour, which may then be employed to provide reliable estimates of the tumour absorbed dose.…”