Endocrine Abstracts (2006) 11 P820

Application of positron emission tomography (PET) in the study of cerebral glucose uptake in hypothyroid rats: effect of T3 administration

M De Servi1, N Belcari2, J Bernal3, S Refetoff4, P Salvadori5, E Gianetti1, G De Marco1, M Tonacchera1, P Vitti1, A Del Guerra2 & A Pinchera1

1Dep Endocrinology University of Pisa, Pisa, Tuscany, Italy; 2Dep Physics and INFN University of Pisa, Pisa, Tuscany, Italy; 3Istituto de Investigaciones Biomedicas, Madrid, Spain; 4University of Chicago, Chicago, Illinois, United States; 5CNR-IFC, Pisa, Tuscany, Italy; 6Centro di Eccellenza AmbiSEN, Pisa, Tuscany, Italy.

Thyroid hormone (TH) plays a major role in nervous system development. Its deficiency causes severe brain malfunction, which in the human results in cretinism. With the recent availability of new imaging techniques, as small animal PET, it is now possible to study cerebral metabolism in vivo. The aim of this work was to study the in vivo effect of TH on the brain of hypothyroid rats in terms of metabolic function, using PET scanning. For the experiment we used the YAP-(S)PET small animal scanner. As radiotracer we used 2-deoxy-2-(18F)fluoro-D-glucose (FDG). 19 Wistar rats (10 F, 9 M) were maintained in a climate-controlled room on a normal 12 h light/dark cycle with food and water available ad libitum. Thyroid hormone deficiency was induced in 14/19 by drinking water with antithyroid drugs (MMI 0.02% and KClO4 1%). To study the effects of TH on the brain, 7/14 rats were treated with 50 ug of T3 injected i.p. for 3 consecutive days in 5 rats and for 6 consecutive days in 2 rats. The PET scanning was done the 4th and 7th day. The day before the experiment the rats were fasted but allowed free access to water. The rats were anaesthetized with a mixture of ketamine and xylazine. In each rat we injected i.v. 1,4 mCi of [18F]FDG. We started PET scanning 30 minutes after [18F]FDG injection. The images showed a clear resolution of several brain structures: we distinguished the cerebral cortex, the neostriatum, the thalamus, the cerebellum and the olfactory bulbs. The [18F]FDG uptake value obtained in different brain areas were normalized to body surface and brain weight of the animals. The TSH levels were high in hypothyroid rats and not detectable in T3-treated rats (P=0.002). There was a statistically significant difference between cerebral glucose uptake in hypothyroid rats with respect T3-treated rats but, contrary to what expected, the glucose uptake was higher in hypothyroid rats. No differences were found between male and female and the duration of treatment with T3. In conclusion, a) we developed a new methodology to study the effects of TH on the brain in vivo; b) contrary to what expected, the glucose uptake was higher in hypothyroid rats than in T3-treated rats.