Riassunto analitico
Monocarboxylate transporters (MCTs) are proton-linked transmembrane protein and essential metabolites in mammalian cells. Among them, MCT1 and MCT4 create a lactate shuttle that maintains the lactate homeostasis among cells. These transporters are overexpressed in several cancer types and play an important role in cancer development, proliferation and survival. The inhibition of these transporters has been demonstrated to be a new strategy for the treatment and diagnosis of solid cancers. The characteristics of these transporters, as well as their high expression in cancer cells, make them ideal targets for selective imaging in vivo; therefore, radiolabeled inhibitors of MCT1-4 are potential imaging agents for cancer diagnosis using positron emission tomography (PET). In recent years, several MCT1 inhibitors have been developed but only few of them are known with clinical potential and have been radiolabeled. Since 18F is one of the most important radionuclides for PET, in this work, fluorinated derivatives of new potential inhibitors of MCT1, based on diclofenac analogues and 7-substituted carboxycoumarin structures, have been developed. Moreover, suitable corresponding labeling precursors have been developed in order to optimize the labeling strategy and labeling conditions. A 7-substituted carboxycoumarin derivative has been successfully labeled and primarily characterized, while new possible precursors and fluorinated analogs have been suggested for the other structures.
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