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Browsing by Subject "Radiolabel stability assays"

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  • Ambrosio Macias, Natalia Isabel (2024)
    Positron emission tomography (PET) is a tomographic imaging technique based on the administration of a positron-emitting radionuclide attached to a targeting molecule to monitor diverse biochemical and cellular processes in living subjects by obtaining three-dimensional images of the spatial distribution and concentration of the radionuclide activity. 52Mn is a very promising tool for PET imaging, since it decays by EC, β+ (100%) to 52Cr and has favorable physical characteristics such as a half-life of 5.59 days that allows to study long physiological processes and broadens the possibilities for radiolabeling, and a β+ maximum energy of 575 keV, comparable to that of 18F (640 keV), which enhances image resolution. The aim of this thesis has been to analyze the production of 52Mn via proton irradiation using a small medical cyclotron and to achieve the production and separation of the radionuclide in sufficient quantity to be able to carry out preclinical PET studies. 52Mn is easy to produce via proton irradiation of natural chromium in a low energy range. Chromium has four naturally occurring isotopes, of which 52Cr is the most abundant with 83.8%, therefore, a natural Cr target is the most viable and affordable option to produce 52Mn; although the possible reactions of the other isotopes present have to be considered, since each of the byproducts represents a potential contaminant of the final product; for the scope of this work, the main contaminant is 54Mn (t1/2 = 312.2 d). An irradiation conditions optimization for 52Mn production in the IBA Cyclone 10/5 medical cyclotron at the University of Helsinki was performed by analyzing parameters such as beam current, irradiation time, nuclear cross-section and target mounting configurations. 52Mn was produced via the reaction natCr(p,n)52Mn. The activity produced in the test irradiations performed was extracted by solid phase extraction (SPE) ion exchange chromatography with a load-wash-elute method on Dowex 1X8 anion exchange resin 50-100 mesh, where the final product was obtained in the form of manganese chloride [52Mn]MnCl2. The efficiency of the 52Mn extraction procedure was evaluated according to the percentage of activity recovered after it, which was on average 71.80%. It was confirmed that 54Mn is extracted in a fraction very close (66.37%) to that of 52Mn, at least for the type of SPE that was performed in this work. 52Mn was extracted from the irradiated Cr target in sufficient quantity to be able to perform a radiolabeling test of 1,2-Cyclohexylenedinitrilotetraacetic acid (CDTA). Radiolabel stability assays were done in rat serum and cerebrospinal fluid at physiological conditions, and quality control was performed using radio-TLC and autoradiography. The radiolabeled complex showed excellent radiochemical purity up to 48 hours in both media.