Evaluation of renal glucose uptake with [¹⁸F]FDG-PET: Methodological advancements and metabolic outcomes

Studying renal glucose metabolism non-invasively in humans is an unmet need. Positron emission tomography (PET) is the current gold standard for measuring regional tissue glucose uptake rates, but the most widely used glucose analog ([¹⁸F]FDG) is not a good substrate for sodium-glucose cotransporters (SGLTs). As a consequence, [¹⁸F]FDG spills over into the urine and [¹⁸F]FDG-PET considerably underestimates published rates of whole renal glucose uptake obtained using the arterial-venous difference technique. Our aim was to assess whether [¹⁸F]FDG-PET can be used in the study of renal glucose metabolism in humans.

We measured individual [¹⁸F]FDG radioactivity in the urine and estimated intraluminal [¹⁸F]FDG radioactivity concentration; these values were used to correct renal [¹⁸F]FDG-PET data acquired ∼90 min from tracer injection under fasting conditions and during an insulin clamp in 9 lean and 16 obese subjects.

We found that the corrected glucose uptake is consistently higher in the medulla than cortex and that both cortical and medullary glucose uptake are higher in lean than obese participants under both fasting and insulinized conditions. Moreover, cortical but not medullary glucose uptake is increased from the fasting to the insulinized condition.

The data show for the first time that [¹⁸F]FDG-PET can still provide relevant physiological information on regional renal glucose uptake on the condition that [¹⁸F]FDG uptake is corrected for tubular radioactivity.