Browsing by Author "Valdes Portas, Patricia"

The Fukushima-Daiichi Nuclear Power Plant (FNDPP) accident on March 11, 2011, resulted in the release of radioactive cesium-rich microparticles (CsMPs), which can travel long distances thanks to their small size and light weight. Since the long-term radiobiological health-effects and accumulated radiation dose of inhaled CsMPs remain unknown, this thesis proposes a model for tracking synthetic 44-μm and 2.2-μm borosilicate microparticles, which resemble the SiO2 composition and spherical morphology of CsMPs, under Positron Emission Tomography (PET) by radiolabeling them with positron-emitting radionuclides. The use of 44-μm microparticles was discontinued early on as the size of the 2.2-μm particles was more representative of the more common type A CsMPs (0.1-10 μm). Three different radiolabeling approaches were pursued along this project, two directed at 68Ga-labeling, and a third one at 18Ffluorination. The first and main approach was based on the surface functionalization of the particles with (3-aminopropyl)triethoxysilane (APTES) and a suitable chelator for the coordination of [68Ga]Ga3+ ions, like 2,2′-(7-(1-carboxy-4-((4-isothiocyanatobenzyl)-amino)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (p-NCS-Bn-NODAGA) or desferrioxamine (DFO). The second approach involved surface functionalization with ethanolamine, polyethylene glycol (PEG) and DFO. The third approach was based on the natural ability of [18F]F- to substitute silanol groups present on the surface of the borosilicates. Surface functionalization with APTES was confirmed using X-ray photoelectron spectroscopy (XPS), zeta potential and elemental analysis, as opposed to functionalization with PEG-ethanolamine. Scanning electron microscopy (SEM) images showed no significant morphological alterations upon functionalization. 68Ga-labeling of the NODAGA-APTES functionalized 2.2-μm borosilicates was achieved with a mean radiochemical yield (RCY) and radiochemical purity (RCP) of 65 ± 5% and 94 ± 2%, respectively. 68Ga-labeling of DFO-APTES and DFO-PEG-ethanolamine functionalized 2.2-μm borosilicates was not successful (RCY below 15% and RCP of about 50%). 18F-fluorination was not successful due to the high tendency of [18F]F-Si bonds to undergo hydrolysis in aqueous media. The stability of the final [68Ga]Ga-NODAGA-APTES product over a 0-3 hour time period was higher than 90% in five different simulated physiological conditions. The results of this project serve as a promising prospect for the design of radiotracers resembling CsMPs for PET tracking upon in vivo administration.