[In vivo visualization of neurotransmitter function in the human brain by PET].
Measurement of cerebral blood flow and energy metabolism using PET with 15O and 18F labeled tracers allows quantitative evaluation of cerebral metabolism that can be perturbed in pathological states. Neurotransmission is a new target that is visualized by labeling of substrates of enzymes that are involved in neurotransmitter synthesis or degradation. Neuronal receptors are mapped by introducing the labeled ligands that are specifically bound to the receptors in question. We developed unique tracers that label dopamine D2 or histamine H1 receptors. With other available ligands for the muscarinic cholinergic receptors and [18F] fluorodopa, we started clinical investigations to document the state of neurotransmission in patients with epilepsy, Parkinson's disease and dementia. Using [11C] doxepin we observed an increase of H1 receptors in the epileptic foci that showed decreased glucose metabolic rate at the interictal phase. This phenomenon is compatible with reported increase of mu opiate receptors in the brains of epileptic patients. Brain uptake of FDOPA (Ki), calculated by the graphical plot was found relatively stable with age both in the normal population and dementia patients. However, the striatal Ki of FDOPA of severely demented patients significantly reduced, compared with the normal aged subjects. The correlation analysis between FDOPA Ki and severity of dementia as assessed by mini-mental state examination revealed a significant reduction of Ki associated with the disease progression. Increase in D2 receptor density as assessed by the uptake of YM 09151-2 was observed in cases with reduced FDOPA uptake, which may correspond to the state of supersensitivity of the D2 receptors.
Itoh
M
M
Division of Nuclear Medicine, Tohoku University.
Yanai
K
K
Yamaguchi
S
S
Fujiwara
T
T
Nagasawa
H
H
Yokoyama
H
H
Iinuma
K
K
Ido
T
T
D001921:Brain / Q000000981:diagnostic imaging*; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000378:metabolism; D009435:Synaptic Transmission; D014055:Tomography, Emission-Computed
D018377:Neurotransmitter Agents; D017448:Receptors, Dopamine D2; D011969:Receptors, Histamine H1; D004298:Dopamine