NIS: GPS for Cells and Viruses
Quantitative, High-Resolution 3D Imaging, Translatable to the Clinic
NIS is the sodium iodide symporter. It is expressed endogenously in the thyroid, salivary glands, gastric mucosa and mammary glands of mammals, from mice to humans (and everything in between). Its physiological function is to concentrate iodine in the circulation for the synthesis of thyroid hormones. For more than 70 years, NIS has been exploited in the nuclear medicine to provide diagnosis of thyroid disorders. Humans typically received 5 mCi of radioiodine (I-123, gamma emitting isotope) and a planar gamma scan allows rapid diagnosis in the clinical setting. Besides an imaging gene, NIS is being used as cytotoxic gene whereby I-131 (a beta emitting isotope) is given to ablate hyperactive thyroids.
How does NIS reporter gene imaging work?
The target cell can be made to stably express NIS by using a lentiviral vector to deliver the NIS reporter gene. Imanis Life Sciences provides a panel of ready-to-use high-titer lentiviral vectors encoding NIS from various animal species. In some instances (e.g. cancer cell lines for oncology models), high NIS expressing clones can be selected from the mixed cell population using antibiotic selection (neomycin or puromycin lentivectors are available). Once the target cells are confirmed to express NIS (through I-125 uptake assay), the cells can be implanted in vivo to enable longitudinal tracking of the cell fate through SPECT or PET imaging.
Why is NIS superior?
1. Non-immunogenic self protein: permits long term cell monitoring (i.e., if the target cell survives). Human, pig, dog, rat and mouse NIS lentiviral vectors are available exclusively from Imanis.
2. Readily available radioisotopes: off the shelf and ready to use. SPECT tracers include I-125 (mice), I-123, Tc-99m pertechnetate and PET tracers include I-124 and F18-tetrafluoroborate.
3. Reduce costs while providing more meaningful data. It is a more responsible way to do research. By repeat imaging of the same animal longitudinally, fewer animals are needed Also monitors change over time in the same animal for long term studies.
4. Simple to use! Once the NIS cells or vectors are injected into the animal, wait for the desired timepoint, administer the isotope to the animal, image 1-2 hours later on the scanner.
5. True tomographic data. Provides spatial information and unparalleled clarity on the location of the signals.
Real life examples of NIS in action
Longitudinal NIS Imaging of Transplanted Primary Hepatocytes Learn More Here
Noninvasive 3D imaging of liver regeneration in a mouse model of hereditary tyrosinemia type 1 using the sodium iodide symporter gene. Hickey et. al., Liver Transplantation. 2014 Dec 6. In press. PMID: 25482651.
In this landmark study, Dr. Hickey and colleagues transduced primary murine hepatocytes with a lentiviral vector encoding murine NIS, confirmed NIS expression and function in vitro, and transplanted the NIS expressing primary hepatocytes into congenic FAH-/- knockout transgenic mice. Transplantation of the lentiviral transduced hepatocytes were functional and prevented liver failure. Importantly, the engraftment and repopulation of the hepatocytes can be imaged longitudinally over time (over 80 days) in the same immunocompetent host, enabling for the first time, high resolution and 3D modeling of the patterns of hepatocyte transplantation and engraftment in this model of liver failure.
Longitudinal NIS Imaging of Virus Replication in Tumors Learn More Here
Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy. Miller et al., Molecular Therapy-Oncolytics. Open access. Published online
In this study, Dr. Miller and colleagues developed a highly innovative system using NIS and very high-resolution noninvasive in vivo microSPECT/CT imaging system to determine the intratumoral distribution of an oncolytic VSV virus encoding NIS (VSV-mIFNb-NIS).
Using this method of 3D imaging, the authors show that the labor intensive and time consuming method of serial section and traditional immunohistochemical staining for the VSV viral protein is a thing of the past.
The figure on the right clearly shows the need for 3D imaging when comparing tumors from multiple animals. (a/d) Immunohistochemical staining of tumors shows extensive VSV infection (anti-VSV, green) throughout the tumor (Hoechst, blue). (b/e) Singular SPECT/CT planes taken at the same relative position within the same tumors as those stained in a/d show similar distribution relative to each other (top) but different planes through the same tumors at another location show different distributions. (c/f) 3D space filling allows differences in distribution to be clearly appreciated where tumor on top has decreased voids compared to tumor on bottom. (Molecular Therapy-Oncolytics).