Abstract
Preclinical and clinical tomographic imaging systems increasingly are being utilized for non-invasive imaging of reporter gene products to reveal the distribution of molecular therapeutics within living subjects. Reporter gene and probe combinations can be employed to monitor vectors for gene, viral, and cell-based therapies. There are several reporter systems available; however, those employing radionuclides for positron emission tomography (PET) or singlephoton emission computed tomography (SPECT) offer the highest sensitivity and the greatest promise for deep tissue imaging in humans. Within the category of radionuclide reporters, the thyroidal sodium iodide symporter (NIS) has emerged as one of the most promising for preclinical and translational research. NIS has been incorporated into a remarkable variety of viral and non-viral vectors in which its functionality is conveniently determined by in vitro iodide uptake assays prior to live animal imaging. This review on the NIS reporter will focus on 1) differences between endogenous NIS and heterologously-expressed NIS, 2) qualitative or comparative use of NIS as an imaging reporter in preclinical and translational gene therapy, oncolytic viral therapy, and cell trafficking research, and 3) use of NIS as an absolute quantitative reporter.
Highlights
Advances in preclinical and clinical tomographic imaging systems have enabled non-invasive imaging of reporter gene products to reveal the temporal and spatial biodistribution of molecular therapies in virtually any location within living subjects
NIS-mediated transport activity in vivo allows the use of standard nuclear medicine imaging modalities including planar gamma-camera and single photon emission computed-tomography (SPECT) using 99mTC, 125I, and 123I, and positron emission tomography (PET) using 124I and 18F-tetrafluoroborate
Advantages of SPECT compared to PET for small animal studies are that SPECT is 1) less expensive, 2) able to image multiple probes labeled with different radiotracers of different energies at one time allowing the visualization of more than one molecular event, 3) ability to use radiotracers that are readily available at on-site pharmacies and that do not require an on-site cyclotron for production
Summary
Advances in preclinical and clinical tomographic imaging systems have enabled non-invasive imaging of reporter gene products to reveal the temporal and spatial biodistribution of molecular therapies in virtually any location within living subjects. Transient and stable NIS expression in nonthyroidal tissues and tumor xenografts stimulates significant iodide uptake in vivo, to a lesser degree than in vitro NIS-mediated uptake, and has led to the use of NIS as an imaging reporter in numerous preclinical and two clinical research protocols [7, 55, 59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106].
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