<p>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.</p><p>An initial finding using frozen section autoradiography of rat brain and spinal cord showed preferential binding of [<sup>11</sup>C]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, [<sup>11</sup>C]cyano-dizocilpine, as a potential PET tracer for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, was studied. The <i>in vivo</i> visualization of specific binding could not be achieved, though <i>in vitro</i> binding demonstrated good specificity and preferential binding to the activated for of the NMDA receptors.</p><p>The use of the glucose analogue [<sup>18</sup>F]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-<sup>14</sup>C]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. [<sup>11</sup>C]Cyano-dizocilpine, [<sup>11</sup>C]4-NMPB, and [<sup>11</sup>C]flumazenil were utilized in autoradiography to evaluate changes in NMDA, mACh, and GABA<sub>A</sub> receptors, espectively, in experimental TBI. Observations showed a global decrease in the binding potential BP) of (i) [<sup>11</sup>C]cyano-dizocilpine acutely and 12 hrs after TBI, and (ii) of [<sup>11</sup>C]4-NMPB at 12 hrs after TBI, and (iii) a decrease in the BP of [<sup>11</sup>C]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.</p>
| Identifer | oai:union.ndltd.org:UPSALLA/oai:DiVA.org:uu-485 |
| Date | January 2000 |
| Creators | Sihver, Sven |
| Publisher | Uppsala University, Department of Neuroscience, Uppsala : Acta Universitatis Upsaliensis |
| Source Sets | DiVA Archive at Upsalla University |
| Language | English |
| Detected Language | English |
| Type | Doctoral thesis, comprehensive summary, text |
| Relation | Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 ; 942 |
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