Turnover of neurotransmitters in the living and functional brain analized by positron emission Tomography

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1) For functional imaging and quantifying glutamate NMDA-type receptor, [3-^<11>C-cyano]MK-801 has been developed. Prior to PET study, affinity and specificity of this newly synthesized ^<11>C-labelled compound were tested, and it gave a quite reasonable result. Then, PET study using this [3-^<11>C-cyano]MK- 801 was pesformed in an ischemic model of rhesus monkey brain. Compared with regional cerebral blood flow (rCBF) measured by use of ^<15>O-labelled water in PET,higher uptake of radioactivity derived from [3-^<11>C-cyano]MK-801 was obtained in the ischemic site of the brain, indicating comparably high glutamate release in this site. Usefulness of [3-^<11>C-cyano]MK- 801 has thus been assessed.2) Two more cases of autistic patients were treated with tetrahydrobiopterin (R-BH_4) for 12 weeks. Before and after the treatment, PET studies were carried out for regional cerebral blood flow (rCBF) , dopamine turnover, and dopamine D_2 receptor binding, using H_2^<15>O,L-^<11>C-DOPA,and N-^<11>C- methylspiperone, respectively. No significant abnormality of rCBF was observed. Dopamine turnover and dopamine D_2 receptor binding were extraordinarily high, and high value of receptor binding was decreased with improvement of clinical symptoms by treatment.3) In drug-naive schizophrenic patients, dopamine turnover rate measured by PET with L-^<11>C-DOPA was tremendously high, and this rate was decreased by clozapine treatment.4) To assess interactions among dopaminergic, acetylcholinergic, glutamatergic, and GABAergic systems in the brain, especially in the depression, Alzheimer's disease and other disorders mentioned above, we started the series of PET studies using hemilesioned monkeys in the dopaminergic pathway.