Multiplexed Single-Cell Measurements of FDG Uptake and Lactate Release Using Droplet Microfluidics

Abstract

Introduction: Glucose utilization and lactate release are 2 important indicators of cancer metabolism. Most tumors consume glucose and release lactate at a higher rate than normal tissues due to enhanced aerobic glycolysis. However, these 2 indicators of metabolism have not previously been studied on a single-cell level, in the same cell. Objective: To develop and characterize a novel droplet microfluidic device for multiplexed measurements of glucose uptake (via its analog 18F-fluorodeoxyglucose) and lactate release, in single live cells encapsulated in an array of water-in-oil droplets. Results: Surprisingly, 18F-fluorodeoxyglucose uptake and lactate release were only marginally correlated at the single-cell level, even when assayed in a standard cell line (MDA-MB-231). While 18F-fluorodeoxyglucose-avid cells released substantial amounts of lactate, the reverse was not true, and many cells released high amounts of lactate without taking up 18F-fluorodeoxyglucose. Discussion: These results confirm that cancer cells rely on multiple metabolic pathways in addition to aerobic glycolysis and that the use of these pathways is highly heterogeneous, even under controlled culture conditions. Clinically, the large cell-to-cell variability suggests that positron emission tomography measurements of 18F-fluorodeoxyglucose uptake represent metabolic flux only in an aggregate sense, not for individual cancer cells within the tumor.