Abstracts

Increased uptake of alpha-[¹¹C]methyl-L-tryptophan (AMT) in cerebral cortex at the site of the epileptic focus is found in up to 60-70% of children with medically intractable epilepsy. Changes in both cellular metabolism of AMT and transport at the blood-brain barrier can result in increased AMT tissue concentration. The purpose of our study is to determine the relative importance of metabolism and transport of AMT by kinetic analysis of cortical areas of increased AMT uptake., AMT PET was obtained in children with medically intractable epilepsy, and a subgroup of 40 children (17- females, 23 males; age-range: 1-17 years) with prominent foci of increased AMT uptake in cerebral cortex were selected for kinetic analysis. AMT tracer concentration values were obtained using 20-60 min post-injection summed PET images. Dynamic brain data (20-60 min) and blood time activity curves (generated using left ventricular arterial input function for first 20 min and venous plasma values for 20-60 min) were used for Patlak analysis. Patlak analysis was performed for cortical regions to calculate the cellular metabolic rate of AMT (k3[apos]) and volume of distribution (VD[apos]), which is related to the rate of transport of AMT across blood-brain barrier. Multiple linear regression analysis was performed with AMT concentration, as the dependent variable and VD[apos] and k3[apos], as independent variables., Values for AMT tissue concentration (0.067 [mu]Ci/cc [underline]+[/underline]0.024 SD vs. 0.061 [mu]Ci/cc [underline]+[/underline]0.025 SD), k3[apos](0.027 [underline]+[/underline]0.009 SD vs. 0.024 [underline]+[/underline]0.009 SD) and VD[apos](0.37 [underline]+[/underline] 0.12SD vs. 0.35 [underline]+[/underline]0.10) were all higher in epileptic cortex compared to contralateral normal cortex. The tissue AMT concentration was highly correlated (p[lt]0.01) with both k3[apos] and VD[apos] in both normal and epileptic cortex., Our kinetic study suggests that increases in both metabolism and transport of AMT are related to increased AMT concentration in epileptic cortical regions. Future studies employing compartmental modeling of full brain tissue and blood time activity curves are needed to more fully characterize the relative contribution of transport and metabolism in normal and epileptic tissue., (Supported by NIH Grant RO1 NS45151 (to Dr. D.C. Chugani).)