Journal
ANALYTICA CHIMICA ACTA
Volume 1167, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.aca.2021.338593
Keywords
Fluorogenic probe; GLUT1 inhibitor; Tumor diagnosis; Triple-negative breast cancer
Categories
Funding
- National Natural Science Foundation of China [NSFC 21772144]
- National Key Research & Development (R&D) Program of China [2020YFA0907903]
- Tianjin Major Science and Technology Project, China [12ZCDZSY11500]
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A new strategy using a non-antibody GLUT1 binding probe for Warburg effect-based tumor detection and diagnostic imaging has been developed, offering advantages such as high tumor selectivity and fluorescence stability. This approach shows potential for glycolysis-based diagnostic imaging in triple-negative breast cancer, where current FDG/PET diagnosis may be unsatisfactory.
Increased expression of glucose transporters, especially GLUT1 has been proven to be involved in the Warburg effect. Therefore, GLUT1-targeted oncological approaches are being successfully employed for clinical tumor diagnostic imaging (e.g. the F-18-FDG/PET), drug delivery and novel anticancer drug development. Despite the long history of the Warburg effect-targeted cancer diagnosis, other than antibody labeling, there have been no imaging tools developed for direct detection of the GLUT1 expression. Herein, we report the new strategy of using a non-antibody GLUT1 binding probe for Warburg effect-based tumor detection and diagnostic imaging. By specifically inhibits the transport function of GLUT1, the newly designed fluorescent probe, CUM-5, was found to be a useful tool not only for sensitive GLUT1-mediated cancer cell detection, but also for cell-based high-throughput GLUT inhibitor screening. In in vivo studies, CUM-5 shows clear advantages including desirable tumor-to-normal tissue contrast and excellent tumor selectivity (Tm/Bkg and Tm/Torg), as well as high fluorescence stability (long response time) and ideal physiological biocompatibility. In particular, the GLUT1 inhibitor probe offers the potential use for glycolysis-based diagnostic imaging in triple-negative breast cancer which is claimed to have unsatisfactory results with FDG/PET diagnosis, thus remaining a highly metastatic and lethal disease with a need for sensitive and precise identification. (C) 2021 Elsevier B.V. All rights reserved.
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