Increased Cerebral Uptake of [¹⁸F]Fluoro-Deoxyglucose but not [1-¹⁴C]Glucose Early following Traumatic Brain Injury in Rats

Abstract

Following experimental and clinical traumatic brain injury (TBI), the local cerebral metabolic rate of glucose (lCMR(Glc)) is commonly estimated using the 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) method. The adequate estimation of lCMR(Glc) using FDG requires a correction factor, the lumped constant (LC), to convert FDG net uptake into lCMR(Glc). The LC, and thus lCMR(Glc) calculations, require a steady-state that may be disrupted following TBI. In the present report, we hypothesized that [1-(14)C]glucose uptake would accurately reflect glucose dynamics early post-injury, and was compared to the regional uptake of FDG in 44 rats subjected to moderate (2.4-2.6 atm) lateral fluid percussion brain injury (FPI) or sham injury. Cortical energy state and adenylate (ATP, ADP, and AMP) levels were also measured. Early (7-42 min) after FPI, FDG uptake was increased in the ipsilateral cortex and hippocampus (p < 0.05). In contrast, no change in [1-(14)C]glucose uptake (7 and 17 min post-injury) or cortical adenylate content (42 min post-injury) was observed. At 12 h following FPI, the ipsilateral FDG and [1-(14)C]glucose uptake were decreased in the cortex and hippocampus, and the ipsilateral cortical ATP concentration was decreased in comparison to sham-injured controls (p < 0.05). Under the present experimental conditions, the rate of cerebral uptake of FDG and of [1-(14)C]glucose differed, and indicated that following TBI, regional changes in the LC may occur in the immediate, but not in the late, post-injury phase. These results should be considered when interpreting results obtained using FDG for the estimation of lCMR(Glc) early following experimental TBI.

FDG-PET imaging in mild traumatic brain injury: a critical review

“…However, TBI can result in abnormal physiologic conditions and the LC may vary significantly after TBI. Marklund et al provides evidence that the LC in rats changes regionally immediately after TBI (Marklund et al, 2009). Likewise, Wu et al also show a significant decrease in global LC from 0.65 ± 015 to 0.43 ± 0.19 in humans following TBI (Wu et al, 2004a).…”

Lactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations

“…83,84 Changes in the lumped constant were proposed to explain the greater rise in calculated CMR glc when assayed with [ 18 F]fluorodeoxyglucose compared with [1-14 C]glucose after TBI. 85 Unfortunately, the authors did not measure glucose levels in their brain extract samples used to measure ATP, ADP, and AMP. They could have estimated the value for lambda even if glucose was not in a true steady-state after injury (brain glucose half life is 1.5 minutes 86 ).…”