Abstract. To design a potent agent for positron emission tomography/magnetic resonance imaging (PET/MRI) imaging and targeted magnetic hyperthermia-radioisotope cancer therapy radiolabeled surface modifi ed superparamagnetic iron oxide nanoparticles (SPIONs) were used as nanocarriers. Folic acid was conjugated for increasing selective cellular binding and internalization through receptor-mediated endocytosis. SPIONs were synthesized by the thermal decomposition of tris (acetylacetonato) iron (III) to achieve narrow and uniform nanoparticles. To increase the biocompatibility of SPIONs, they were coated with (3-aminopropyl) triethoxysilane (APTES), and then conjugated with synthesized folic acid-polyethylene glycol (FA-PEG) through amine group of (3-aminopropyl) triethoxysilane. Finally, the particles were labeled with 64 Cu (t 1/2 = 12.7 h) using 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono (N-hydroxy succinimide ester) DOTA-NHS chelator. After the characterization of SPIONs, their cellular internalization was evaluated in folate receptor (FR) overexpressing KB (established from a HeLa cell contamination) and mouse fi broblast cell (MFB) lines. Eventually, active and passive targeting effects of complex were assessed in KB tumor-bearing Balb/C mice through biodistribution studies. Synthesized bare SPIONs had low toxicity effect on healthy cells, but surface modifi cation increased their biocompatibility. Moreover, KB cells viability was reduced when using folate conjugated SPIONs due to FR-mediated endocytosis, while having little effect on healthy cells (MFB). Moreover, this radiotracer had tolerable in vivo characteristics and tumor uptake. In the receptor blocked case, tumor uptake was decreased, indicating FR-specifi c uptake in tumor tissue while enhanced permeability and retention effect was major mechanism for tumor uptake.
Success criteria analysis plays a key role in the development of realistic probabilistic safety/risk assessment (PSA/PRA) model because it provides supporting information regarding the response of complex nuclear power plant systems to different accident conditions. The current paper performs plant specific success criteria analysis for steam generator tube rupture (SGTR) accident in a typical pressurized water reactor (PWR) and demonstrates implementation of the obtained best estimate results on a risk model which has been initially developed based on expert judgment and general plant design data. The modifications on the risk model include configuration of the safety systems as well as the event tree structure. The updated PSA model shows 50% reduction in the plant core damage frequency (CDF) in comparison to the base case risk model. This highlights the importance of success criteria analysis for the development of a realistic PSA model in risk informed applications.
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