Assistant Project Scientist
Department of Medicine

Project title: The role of sodium-dependent glucose transport in early-stage lung adenocarcinoma: diagnostic and therapeutic implications

Steven Dubinett, MD - UCLA
David Shackelford, PhD - UCLA
Jorge Barrio, PhD - UCLA
Ernest Wright, PhD - UCLA
Thomas Graeber, PhD - UCLA
Dean Wallace, MD - UCLA
David Elashoff, PhD - UCLA

Multidisciplinary Expertise:
PET Imaging, Oncology, Cancer Metabolism, Translational Research, Pre-clinical Trials in Mouse Models, Lung Pathology, Lung Carcinogenesis.

Project Description:
My project is focused on the role of sodium-dependent glucose transporter 2 (SGLT2) in early-stage lung adenocarcinoma. SGLT2 functions independently of the widely described glucose transporter (GLUT) system, and represents a previously unknown means for malignant cells to sustain their increased need for glucose. My preliminary studies have shown that SGLT2 is expressed in pre-neoplastic and early-stage lung adenocarcinoma (LADC). This is important because high-resolution computed tomography (CT) is very sensitive in detecting early-stage, asymptomatic lung lesions, but it is not specific and cannot distinguish between benign and malignant lesions. Positron-emission tomography (PET) with 2-[F] fluoro-2-deoxyglucose (F-FDG), which detects GLUT activity, is used to stage advanced ADC, but cannot effectively detect early lesions; however, F-FDG does not measure SGLT activity. To study SGLT-mediated glucose transport in pre-malignancy and early-stage lung adenocarcinoma, we use a radio-labeled positron emission tomography (PET) probe, methyl-4-[F] fluorodeoxyglucose (F-Me4FDG), specific for SGLTs. This novel tracer has the potential to complement F-FDG in the diagnosis of early-stage lung tumors. In addition, F-Me4FDG PET can be used to identify SGLT2-active tumors, which may be targeted using FDA-approved SGLT2 inhibitors, the gliflozins. I am going to carry on a pre-clinical validation of F-Me4FDG PET as a translational imaging-based platform to non-invasively identify pre-malignancy and early-stage SGLT2-active lung tumors likely to benefit from treatment with gliflozins.