Tumor hypoxia diagnosis is extremely important for the accurate cancer treatment, since some type of somatic lesions have negative prognosis. Amongst the hypoxia diagnostic tools, molecular PET is the most sensitive method and non-invasive once it uses radiotracers bearing specific reactive groups that exploits differences between the reducing potential of a tumor microenvironment in normoxia and hypoxia. The present work aims to identify new molecular probes for hypoxia tumors diagnosis from a quinazoline core, which is a privileged structure in cancer treatment. The target quinazoline-based compounds (series A and B) comprise two different functional motifs, the bioreductive (2-nitroimidazole) and the radiotracer (radionuclide 18F), switching at C-4 and C-6 positions of the quinazoline ring. Regarding the radiotracer motif, classical fluor-ethylene and trifluoroborate groups along with Copper(I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) reactions (Click Chemistry strategy) will enable the synthesis of a small set of potential probes. Moreover, we also have proposed the synthesis a derivative without the quinazoline scaffold in order to evaluate its biological impact/influence in the absence of the quinazoline core when compared to the quinazoline derivatives. The synthesized compounds will be then evaluated toward their stability in mouse plasma, PET/CT imaging and biodistribution, partition coefficients and in vitro cell uptake.
News published in Agência FAPESP Newsletter about the scholarship: