The Sodium Iodide Symporter (NIS) as an Imaging Reporter for Gene, Viral, and Cell-based Therapies

Penheiter, Alan R.; Russell, Stephen J.; Carlson, Stephanie K.

doi:10.2174/156652312799789235

Cited by 113 publications

(63 citation statements)

References 164 publications

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“…injection of 500 µCi (18.5 MBq) of 99m Tc-pertechnetate, a gamma emitter that is also transported by NIS [24], 99m Tc-pertechnetate accumulation was assessed using a gamma camera equipped with a low-energy high-resolution collimator (e.cam, Siemens, Munich, Germany). Imaging studies were performed under inhalational anesthesia using an isoflurane vaporizer.…”

Section: Methodsmentioning

confidence: 99%

“…We and others have shown the potential of NIS as a reporter gene for molecular imaging with a broad range of possible applications [13,14,15,16,17,18,19,20,21,22,23,24]. In our previous work, the role of NIS as a reporter gene allowed noninvasive multimodal imaging of functional NIS expression by 99m Tc or 123 I scintigraphy as well as SPECT and 124 I PET imaging that correlated well with the results of ex vivo gamma counter measurements as well as NIS mRNA and protein analysis.…”

Section: Introductionmentioning

confidence: 99%

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Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Schmohl¹,

Müller²,

Schwenk³

et al. 2015

Eur Thyroid J

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Due to the high variance in available protocols on iodide-131 (¹³¹I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of ¹³¹I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T₄ concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and ^99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) ¹³¹I alone was not sufficient to abolish thyroidal T₄ production, 500 µCi (18.5 MBq) ¹³¹I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high ¹³¹I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) ¹³¹I decreased serum T₄ concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. ^99mTc-pertechnetate scintigraphy revealed absence of thyroidal ^99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Schmohl¹,

Müller²,

Schwenk³

et al. 2015

Eur Thyroid J

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“…NIS is also used as a reporter gene in small and large animal imaging studies and in humans to monitor the pharmacokinetics and fate of gene, cell and virus therapies 2 . Several readily available SPECT or PET tracers, I-123, I-125, I-124 and Tc-99m pertechnetate, are compatible with NIS imaging.…”

Section: Introductionmentioning

confidence: 99%

Oral contrast enhances the resolution of in-life NIS reporter gene imaging

et al. 2013

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NIS reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we report that orally administered barium sulfate enhances CT definition of the stomach, masks background gamma ray emissions from the stomach, and enhances signal detection from radiotracer uptake in NIS-transduced organs.

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“…For longer term reporting on vector distribution other methods are available. For example, the sodium iodide symporter (NIS) is a well-known and extensively studied reporter gene, and NIS cDNA can be contained within the AAVrh.10 capsid373839. This and other reporter gene methods require a few weeks to be expressed and so can only be assessed in that timeframe.…”

Section: Discussionmentioning

confidence: 99%

Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors

Kothari

et al. 2017

Sci Rep

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Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.

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The Sodium Iodide Symporter (NIS) as an Imaging Reporter for Gene, Viral, and Cell-based Therapies

Cited by 113 publications

References 164 publications

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Oral contrast enhances the resolution of in-life NIS reporter gene imaging

Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors

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