Determination of Functional Activity of Sodium Glucose Transporters in Cancer
- Author(s): Silverman, Matthew John
- Advisor(s): Barrio, Jorge R
- Liao, James C
- et al.
As cancer incidence continues to rise in the United States, there remains an increasing demand for new tools for oncologists to use for both diagnosing and directing treatments for cancer. Among these tools, Positron Emission Tomography (PET) has been rising in prominence in recent decades as a useful tool for monitoring the metabolic activity of organs and tissues in vivo. Unlike Computed Tomography (CT), Magnetic Resonance Imaging (MRI) or Ultrasound (US), PET imaging allows medical professionals and researchers to use molecular imaging probes to measure metabolic activity of tissues, opening up a different dimension of medical evaluation. In PET imaging for cancer, 2-deoxy-2-[F-18]fluoro-D-glucose (2-FDG) has been the historically dominant molecular probe used, since 2-FDG uptake occurs via facilitative glucose transporters (GLUTs), and its tissue accumulation reflects hexokinase (HK) activity in proportion to the glucose metabolic rate. In many cancers, glucose utilization through these transporters increases dramatically relative to non-cancerous tissue, making 2-FDG a valuable molecular imaging probe in detecting and monitoring the progression of cancer. However, there are some cancers that don't show consistently increased 2-FDG uptake, rendering 2-FDG PET less effective in these situations for medical diagnosis. Recent work has suggested the possibility that another class of glucose transporters, sodium glucose transporters (SGLTs), is expressed and active in a variety of cancers. SGLT activity, which cannot be measured by 2-FDG PET, could offer an explanation as to why 2-FDG accumulation seems less significant in some cancers. While there have been several publications examining mRNA and protein SGLT expression in cancer, there has yet to be any data confirming functional SGLT activity in vivo. In this work, we present initial data on the functional activity of SGLTs in cancerous cells from both prostate and pancreatic cancer both in vitro and in vivo. Using methyl-4-deoxy-4-[F-18]fluoro-D-glucopyranoside (Me-4FDG), a PET molecular imaging probe specific for SGLTs, we identify SGLT activity in cancer cell lines, animal tumor xenografts, and human tumors. These results usher in the novel possibility of utilizing SGLT PET imaging molecular imaging probes for diagnosing and characterizing cancerous tumors.