A new PET probe, F-18-tetrafluoroborate, for the sodium/iodide symporter: possible impacts on nuclear medicine
ABSTRACT As early as 1915, it was found that iodide is required in the thyroid gland for the production of thyroid hormones. Since then, radioiodines have been used as tracers in thyroid function tests and as agents for the treatment of hyperthyroidism and benign thyroid diseases. Furthermore, knowledge of the importance of the role played by iodine transport in thyroid cancer cells provides the rationale for the use of radioiodines to diagnose and treat thyroid cancer (1, 2). In fact, the clinical utilization of radioiodines led to the birth of nuclear medicine. Today, it is known that the iodide pump is a sodium/iodide symporter (NIS), an intrinsic membrane protein of the thyroid gland follicular cells (3, 4), and that the NIS-catalysed accumulation of iodide in cells from the interstitium is achieved against its transmembrane electrochemical gradient, which is maintained by sodium-potassium adenosine triphosphatase. The identification of the human NIS (hNIS) gene created many new diagnostic and therapeutic opportunities, and in particular, researchers are currently investigating the use of hNIS as a reporter gene for gene therapy and molecular and genomic imaging (5).
Full-textDOI: · Available from: Hyewon Youn, Mar 20, 2015
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- "For the comparison of F-18 and I-124 in animal studies, F-18 TFB was used. Like the negative ion I-124, TFB radiolabelled with F-18 is transported by the human sodium iodide symporter (hNIS) , . "
ABSTRACT: Small animal Positron Emission Tomography (PET) should provide accurate quantification of regional radiotracer concentrations and high spatial resolution. This is challenging for non-pure positron emitters with high positron endpoint energies, such as I-124: On the one hand the cascade gammas emitted from this isotope can produce coincidence events with the 511 keV annihilation photons leading to quantification errors. On the other hand the long range of the high energy positron degrades spatial resolution. This paper presents the implementation of a comprehensive correction technique for both of these effects. The established corrections include a modified sinogram-based tail-fitting approach to correct for scatter, random and cascade gamma coincidences and a compensation for resolution degradation effects during the image reconstruction. Resolution losses were compensated for by an iterative algorithm which incorporates a convolution kernel derived from line source measurements for the microPET Focus 120 system. The entire processing chain for these corrections was implemented, whereas previous work has only addressed parts of this process. Monte Carlo simulations with GATE and measurements of mice with the microPET Focus 120 show that the proposed method reduces absolute quantification errors on average to 2.6% compared to 15.6% for the ordinary Maximum Likelihood Expectation Maximization algorithm. Furthermore resolution was improved in the order of 11-29% depending on the number of convolution iterations. In summary, a comprehensive, fast and robust algorithm for the correction of small animal PET studies with I-124 was developed which improves quantitative accuracy and spatial resolution.IEEE Transactions on Nuclear Science 02/2014; 61(1):142-153. DOI:10.1109/TNS.2013.2293914 · 1.28 Impact Factor
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- "The drawbacks associated with use of 124I are that it is not readily available, its production is complex, and the tissue penetration prior to annihilation of the high energy positrons from 124I decay (maximum positron range of >6 mm) severely limits the spatial resolution in a small animal setting . A recent breakthrough in NIS research is the development of a novel PET probe 18F-tetrafluoroborate ([18F]TFB) [152, 153]. Although not yet widely used, this may replace the less sensitive and lower resolution 124I for PET imaging of NIS. "
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.Current Gene Therapy 02/2012; 12(1):33-47. DOI:10.2174/156652312799789235 · 2.54 Impact Factor
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ABSTRACT: Conventional methods for radiolabelling biomolecules such as proteins and peptides with fluorine-18 for PET imaging rely on carbon-fluorine bond formation and are complex and inefficient. Several non-carbon elements form strong bonds (i.e. with high bond enthalpy) with fluorine, but with lower activation energy for their formation compared to carbon-fluorine bonds, whilst preserving a relatively high kinetic stability. In particular, by incorporating boron-, aluminium- and silicon-containing prosthetic groups into biomolecules, promising results have recently been achieved in the radiolabelling with F-18-fluoride under mild aqueous conditions, affording a level of convenience, efficiency and specific activity potentially superior to those offered by conventional C-F bond formation methods. The promise already shown by these early studies heralds a new branch of bioconjugate radiochemistry involving a wider range of "fluoridephilic" elements for synthesis of PET molecular imaging agents.Dalton Transactions 06/2011; 40(23):6196-205. DOI:10.1039/c0dt01594f · 4.20 Impact Factor