Pilot study of SGLT2 in the characterization of early lung adenocarcinoma

2021

Early Detection Research Award

Claudio Scafoglio, MD, PhD

University of California, Los Angeles

Los Angeles

The protein SGL2 seems to be produced in higher quantities on abnormal lung cells than on normal lung cells. Dr. Scafoglio is testing whether SGL2 can be used to image lung cancer cells by using a new imaging technology.

Research Summary

Lung cancer claims around 140,000 lives in the United States every year; there is great need for early diagnosis strategies, and an attractive target is cancer metabolism. Cancer cells require more glucose than normal tissues for their unregulated growth; glucose cannot enter the cells freely, but needs to be transported by specific proteins called glucose transporters.

We have recently discovered that early-stage and pre-cancerous lesions rely on a specific glucose transporter to satisfy their metabolic needs: sodium-dependent glucose transporter 2 (SGLT2). We have introduced a new probe, Me4FDG, which can be used for positron emission tomography (PET) to detect accumulation of glucose in the patient’s tissues through a whole-body scan. We have started a pilot trial of Me4FDG PET in patients diagnosed with lung cancer as proof of principle that this diagnostic technique can be used for early lung cancer diagnosis. We propose to perform more thorough and systematic studies to evaluate the feasibility of Me4FDG PET as a novel diagnostic imaging technique for early stage lung cancer.

Technical Abstract

Lung cancer is the leading cause of cancer-related death in US, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis is crucial. High-resolution CT has increased the discovery of solitary lung lesions, many of which are benign, whereas some progress to invasive cancer; the identification of novel biomarkers to predict the malignant potential of these lesions is of paramount importance. We found that sodium-dependent glucose transporter 2 (SGLT2) is expressed in human pre-malignant and early-stage LADC, and is required for progression of LUAD. SGLT activity can be measured by PET imaging with methyl-4-[18F] fluorodeoxyglucose (Me4FDG). Importantly, we identified SGLT2 activity in FDG-negative, early-stage lesions in mouse models and in human lung nodules.

Specific aims of the study are: 1. To assess the safety and efficacy of Me4FDG in patients with lung cancer, via a pilot study in 60 patients (30 with pathological diagnosis of LUAD, 30 with a clinical diagnosis of benign nodule); 2. To evaluate the prognostic significance of SGLT2 expression in early lung adenocarcinoma, through SGLT2 staining of 674 samples embedded in tissue microarrays.

The proposed research is likely to introduce a novel diagnostic tool for early diagnosis of lung adenocarcinoma, and further define the prognostic role of SGLT2 in lung cancer. If successful, this pilot trial will open the way for larger clinical studies where we will evaluate the ability of Me4FDG PET to predict the malignant behavior of indeterminate subsolid lung nodules. This will improve the early diagnosis of lung cancer.

Key words

Adenocarcinoma

Early detection

Non-small cell lung cancer (NSCLC)

Pilot study of SGLT2 in the characterization of early lung adenocarcinoma

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