Blood Flow-Metabolism Mismatch: Good for the Tumor, Bad for the Patient

Diagram of quantitative imaging methods used to measure blood flow and metabolism. Native molecules are shown in black lettering, and administered radiopharmaceuticals are shown in red. The delivery of nutrients and oxygen is dependent upon tissue perfusion or blood flow. ¹⁵O-water is a freely diffusible substance whose delivery is limited by blood flow. Dynamic ¹⁵O-water captures the time course of tracer uptake and washout in tissue, from which regional tissue perfusion can be estimated. FDG is a glucose analog that traces glycolysis. After delivery by blood flow and transit across capillaries and cellular membranes, FDG is phosphorylated inside the cell by hexokinase (HK), the rate-limiting step in glycolysis; but FDG is not a substrate for downstream steps in glycolysis. FDG, therefore, is “metabolically trapped” as FDG-6P, at a rate proportional to the glucose metabolic flux. Sequential injections of ¹⁵O-water (t_1/2 ≈ 2 minutes) and ¹⁸F-FDG (t_1/2 ≈ 2 hours) can yield regional estimates of tissue blood flow and glucose metabolism, and the ratio between flow and metabolism.