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- Marklund, Niklas, et al.
(author)
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Increased Cerebral Uptake of [18F]Fluoro-Deoxyglucose but not [1-14C]Glucose Early following Traumatic Brain Injury in Rats
- 2009
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 26:8, s. 1281-1293
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Journal article (peer-reviewed)abstract
- Following experimental and clinical traumatic brain injury (TBI), the local cerebral metabolic rate of glucose (lCMRGlc) is commonly estimated using the 2-[18F]fluoro-2-deoxy-D-glucose (FDG) method. The adequate estimation of lCMRGlc using FDG requires a correction factor, the lumped constant (LC), to convert FDG net uptake into lCMRGlc. The LC, and thus lCMRGlc calculations, requires a "steady state" that may be disrupted following TBI. In the present report, we hypothesized that [1-14C]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, 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 [1-14C]glucose uptake (7 and 17 min) or cortical adenylate content (42 min post-injury) was observed. At 12 hours following FPI, the ipsilateral FDG and [1-14C]glucose uptake was 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 [1-14C]glucose differs, and indicate 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 lCMRGlc early following experimental TBI.
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- Sihver, Sven
(author)
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Development of in vitro and ex vivo positron-emitting tracer techniques and their application to neurotrauma
- 2000
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Doctoral thesis (other academic/artistic)abstract
- The use of positron-emitting tracers has been extended beyond tomographic facilities in the last few years, giving rise to a general positron-emitting tracing technique. The methodological part of the present thesis involved the evaluation of the performance of storage phosphor (SP) plates, with tracers labeled with high-energy, short-lived, positron-emitting radionuclides, using homogenized tissue specimens and autoradiography with frozen brain sections. The SP plates showed superior sensitivity and a linear response over a wide radioactivity range. Autoradioradiography provided reliable results due to (a) adequate sensitivity for low radioactivity concentration, b) an excellent linear range, and (c) satisfactory resolution. Though equilibration time of receptor-ligand interaction was dependent upon section thickness, quantification was possib with thinner sections.An initial finding using frozen section autoradiography of rat brain and spinal cord showed preferential binding of [11C]4-NMPB, a muscarinic acetylcholine (mACh) receptor antagonist, to the M4 subtype of mACh receptors. Further work to ascertain this specificity, by use of binding studies on cell membranes from CHO-K1 cells expressing individual subtypes of human mACh receptors, suggested lack of subtype selectivity. With respect to the possible cliinical use in glutamatergic neuropathology, [11C]cyano-dizocilpine, as a potential PET tracer for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, was studied. The in vivo visualization of specific binding could not be achieved, though in vitro binding demonstrated good specificity and preferential binding to the activated for of the NMDA receptors.The use of the glucose analogue [18F]fluorodeoxyglucose (FDG) to study glucose utilization was evaluated in experimental traumatic brain injury (TBI). A trauma-induced increased uptake of FDG was seen, whereas the uptake of [1-14C]glucose remained unchanged. This discrepancy might be due to the increased postraumatic affinity of FDG for the endothelial glucose transporter proteins and/or to the hexokinase enzyme. [11C]Cyano-dizocilpine, [11C]4-NMPB, and [11C]flumazenil were utilized in autoradiography to evaluate changes in NMDA, mACh, and GABAA receptors, espectively, in experimental TBI. Observations showed a global decrease in the binding potential BP) of (i) [11C]cyano-dizocilpine acutely and 12 hrs after TBI, and (ii) of [11C]4-NMPB at 12 hrs after TBI, and (iii) a decrease in the BP of [11C]flumazenil in the cortex and hippocampus ipsilateral to the site of injury. The demonstrated changes in receptor binding after TBI are indicative of a widely dissipated effect of TBI on the particular neurotransmitter receptor systems as compared with what would be expected from FDG studies after TBI, i.e., a local disturbed neurotransmission.
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