Abstract
The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (19F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that targets the GLUT5 transporter. Inherent fluorescent properties of the coumarin fluorophore allowed us to establish the probe's uptake efficiency and GLUT5-specificity in a GLUT5-positive breast cell line using fluorescence detection techniques. The click chemistry approach employed in the design of the probe enables late-stage functionalization, an essential requirement for obtaining the radiolabeled analog of the probe for future in vivo cancer imaging applications. The high affinity of the probe to GLUT5 allowed for the effective uptake in nutrition-rich media.