Loss of radioactive 2-deoxy-d-glucose-6-phosphate from brains of conscious rats: Implications for quantitative autoradiographic determination of regional glucose utilization

Radioactive glucose and 2-deoxy-d-glucose (deoxyglucose) were compared as tracers for estimating the rate of rat brain glucose utilization after an intravenous injection. The [brain] : [blood] ratio of deoxyglucose content was twice as large as that of glucose at 5 min, 3 times at 45 min, and 13 times at 240 min. While [2-¹⁴C]glucose accounted for about 20% of total brain¹⁴C (acid soluble) at 10 min, labeled deoxyglucose took 45 min to fall to comparable levels. Labeled 2-deoxy-d-glucose-6-phosphate (deoxyglucose phosphate) did not accumulate after 10 min despite the fact that deoxyglucose was available continuously for phosphorylation. This resulted from loss of deoxyglucose phosphate, which was in proportion to its concentration. The disappearance of deoxyglucose phosphate was probably catalyzed by glucose-6-phosphatase, which reacts with deoxyglucose phosphate and which is present in brain.Since the [brain]: [blood] ratio of labeled deoxyglucose increases as time passes and since deoxyglucose phosphate is lost from brain at an appreciable rate, its use for quantitative determination of the rate of rat brain glucose utilization is much more complex than previously realized. Approximately 45 min are necessary to reduce background contamination to acceeptable levels for autoradiography during which time substantial amounts of deoxyglucose phosphate may be lost. The primary reason for using deoxyglucose to measure glucose utilization by the brain is the assumption that deoxyglucose phosphate is lost very slowly from the brain. In view of the fact that loss of deoxyglucose phosphate cannot be ignored, the advantage of labeled deoxyglucose over labeled glucose is open to question.