In conventional PET measurements, a experimental animal is anesthetized and secured to prevent movement. However, the anesthesia affects the several neurotransmissions, for example, dopamine involved in neurotransmission in the brain and also causes unwanted changes in the PET measurement results. Our center, however, uses an animal PET scanner having a gantry tilt mechanism and a special head forlding method so the monkey's brain can be measured in a conscious state. PET testing on monkeys in a conscious non-anesthetized therefore has more value.

Method for measuring brain functions of monkeys in a conscious state allows making a map of brain functions to show what region is activated when using higher brain functions involved in memory, learning, cognition and judgment, etc. By measuring changes in the brain blood flow using [¹⁵O]H₂O, changes in central nervous system activity during task performance can be detected as quantitative images. Besides blood flow in the brain, ongoing research involves activation experiments using [¹⁸F]FDG as an indicator of energy metabolism or using a [¹¹C]-labeled ligand unique to neurotransmitter substances to mark changes in receptor activation as an indicator.

Along with the research into currently used positron-emissive tracers, we are also developing new labeled compounds. These compounds exhibit unusually large characteristics in particular versus muscarinic cholinergic receptors, and besides developing various inductive labeling methods for these new labeled compounds, we are using them to evaluate the dynamic state of a monkey brain to help find novel compounds with optimal qualities to match particular research goals.

Brain function mapping techniques are used to detect localized changes in the brain blood flow rate occurring in designated regions of neural activity during performance. However, little is currently known about the rise in neural activity that brings about the coupling function causing increased blood flow. At the Hamamatsu Photonics PET Center, we clarified how the acetylcholine neural system affects the coupling function in the monkey brain. We also reported on how this coupling function declines with aging and how this decline can be restored with substances that accelerate various cognitive functions in the brain.

Neural activity includes a variety of functions such as biosynthesis, storage, and release of neurotransmitter, and binding, uptake and degradation in the synapse. Different kinds of nerve diseases come about in many cases because some of these functions are abnormal. In order to understand the neuronal mechanism and accurately diagnose and treat these diseases, each of these functions has to be analyzed and understood as part of the total process. At the Hamamatsu Photonics PET Center, we provide special labeled compounds for each of these functions such as in dopamine and serotonin systems.

Although many differences exist in the various biofunctions, the changes found in brain functions among primates and rodents when cerebral ischemia occurs far exceed what we have known up until now. At the Hamamatsu Photonics PET Center we constructed a cerebral ischemic model using a monkey brain which is the experimental animal most resembling humans. Using this model we are studying how deprivation and recirculation of blood flow to the brain affects the neuronal cells. Besides revealing the actual mechanism causing cerebral ischemia, we are making pre-clinical evaluations of potential substances for use in new medicines to treat brain ischemia.

Besides researching the various changes accompanying biological and disease-related senility in the human brain, we have also found the monkey useful as an animal senility model since it most resembles humans. Our PET Center holds aged rhesus monkeys equivalent to 80 year old humans. Here the PET scanner proves extremely effective since it can make repeated measurements with non-invasive test methods. We take full advantage of PET to measure and reveal changes due to aging in brain blood flow, the metabolism and the various central nervous systems and also blood flow reaction in response to stimulation, and explaining these results by comparing them with younger animals.

The spread of drugs such as cocaine, amphetamines, and thinner has become a worldwide problem. The addictive properties of these drugs indicate a correlation between addiction and the dopamine neural system but many points are still unclear. Our animal PET scanner has already shown clear changes in dopamine D1/D2 receptors and dopamine uptake site in the rat brain after administering chronic doses of cocaine. Based on these results, we are now investigating how these addicting drugs affect the brain functions of monkeys by multi-parametric measurements.