Differentiated thyroid cancer (DTC) is usually indolent with good prognosis and long-term survival. However, DTC distant metastasis is often a grave event and accounts for most of its diseasespecific mortality. The major sites of distant metastases are the lung and bone. Metastases to the brain, breast, liver, kidney, muscle, and skin are rare or relatively rare. Nevertheless, recognizing rare metastases from DTC has a significant impact on the clinical decision making and prognosis of patients.131 I single photon emission computed tomography/computed tomography ( 131 I-SPECT/CT) can provide both metabolic and anatomic information about a lesion; therefore, it can better localize and define the 131 I-WBS findings in DTC patients. In this pictorial review, the imaging features of a range of rare metastases from DTC are demonstrated, with a particular emphasis on the 131 I-SPECT/CT diagnostic aspect.
Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma.
Background Functional sugar alcohols have been widely used in the food, medicine, and pharmaceutical industries for their unique properties. Among these, erythritol is a zero calories sweetener produced by the yeast Yarrowia lipolytica. However, in wild-type strains, erythritol is produced with low productivity and yield and only under high osmotic pressure together with other undesired polyols, such as mannitol or d-arabitol. The yeast is also able to catabolize erythritol in non-stressing conditions. Results Herein, Y. lipolytica has been metabolically engineered to increase erythritol production titer, yield, and productivity from glucose. This consisted of the disruption of anabolic pathways for mannitol and d-arabitol together with the erythritol catabolic pathway. Genes ZWF1 and GND encoding, respectively, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were also constitutively expressed in regenerating the NADPH2 consumed during erythritol synthesis. Finally, the gene RSP5 gene from Saccharomyces cerevisiae encoding ubiquitin ligase was overexpressed to improve cell thermoresistance. The resulting strain HCY118 is impaired in mannitol or d-arabitol production and erythritol consumption. It can grow well up to 35 °C and retain an efficient erythritol production capacity at 33 °C. The yield, production, and productivity reached 0.63 g/g, 190 g/L, and 1.97 g/L·h in 2-L flasks, and increased to 0.65 g/g, 196 g/L, and 2.51 g/L·h in 30-m3 fermentor, respectively, which has economical practical importance. Conclusion The strategy developed herein yielded an engineered Y. lipolytica strain with enhanced thermoresistance and NADPH supply, resulting in a higher ability to produce erythritol, but not mannitol or d-arabitol from glucose. This is of interest for process development since it will reduce the cost of bioreactor cooling and erythritol purification.
We report a facile approach to fabricating low-generation poly(amidoamine) (PAMAM) dendrimer-stabilized gold nanoparticles (Au DSNPs) functionalized with folic acid (FA) for in vitro and in vivo targeted computed tomography (CT) imaging of cancer cells. In this study, amine-terminated generation 2 PAMAM dendrimers were employed as stabilizers to form Au DSNPs without additional reducing agents. The formed Au DSNPs with an Au core size of 5.5 nm were covalently modified with the targeting ligand FA, followed by acetylation of the remaining dendrimer terminal amines to endow the particles with targeting specificity and improved biocompatibility. Our characterization data show that the formed FA-modified Au DSNPs are stable at different pH values (5-8) and temperatures (4-50 °C), as well as in different aqueous media. MTT assay data along with cell morphology observations reveal that the FA-modified Au DSNPs are noncytotoxic in the particle concentration range of 0-3000 nM. X-ray attenuation coefficient measurements show that the CT value of FA-modified Au DSNPs is much higher than that of Omnipaque (a clinically used CT contrast agent) at the same concentration of the radiodense elements (Au or iodine). Importantly, the FA-modified Au DSNPs are able to specifically target a model cancer cell line (KB cells, a human epithelial carcinoma cell line) over-expressing FA receptors and they enable targeted CT imaging of the cancer cells in vitro and the xenografted tumor model in vivo after intravenous administration of the particles. With the simple synthesis approach, easy modification, good cytocompatibility, and high X-ray attenuation coefficient, the FA-modified low-generation Au DSNPs could be used as promising contrast agents for targeted CT imaging of different tumors over-expressing FA receptors.
Dendrimer-entrapped gold nanoparticles (Au DENPs) can be formed using low-generation dendrimers pre-modified by polyethylene glycol (PEG). The formed PEGylated Au DENPs with desirable stability, cytocompatibility, and X-ray attenuation properties enable efficient computed tomography imaging of the heart and tumor model of mice.
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