Quantitative Analysis of Amyloid ß Deposition in Patients with Alzheimer’s Disease Using Positron Emission Tomography
Manabu Tashiro (Division of Cyclotron Nuclear Medicine, Tohoku University, Japan), Nobuyuki Okamura (Department of Pharmacology, Tohoku University Graduate School of Medicine, Japan), Shoichi Watanuki (Division of Cyclotron Nuclear Medicine, Tohoku University, Japan), Shozo Furumoto (Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Japan & Department of Pharmacology, Tohoku University Graduate School of Medicine, Japan), Katsutoshi Furukawa (Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Japan), Yoshihito Funaki (Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Japan), Ren Iwata (Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Japan), Yukitsuka Kudo (Innovation of New Biomedical Engineering Center, Tohoku University Hospital, Japan), Hiroyuki Arai (Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Tohoku University, Japan), Hiroshi Watabe (Department of Molecular Imaging in Medicine, Osaka University Graduate School of Medicine, Japan) and Kazuhiko Yanai (Division of Cyclotron Nuclear Medicine, Tohoku University, Japan & Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Japan)
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These findings suggest that [11C]BF-227 is a promising PET probe for clinical evaluation of early Aß deposition in AD patients.
Positron Emission Tomography
Positron emission tomography (PET) is a technique used for functional and molecular imaging based on nuclear medicine technology. Nuclear medicine techniques date back to the early 20th century. Nuclear medicine was originally developed as a “tracer technique” by the Nobel laureate, Dr. George de Hevesy. In our study, the term “tracer” means an extremely small amount of radioisotope that is administered to the subject to permit imaging certain biological phenomena in the living body. A tracer is sometimes also called a “probe”. Probes detect the presence of a certain biological substances in small amounts (often at the “nano-” to “pico-” molar scale) (Tashiro, 2010). The tracer technique was later established as a nuclear medicine technique in the late 20th century, mainly due to advancements in radiolabeling techniques and signal detection devices such as PET.
Using PET, a wide range of biological information can be obtained from the living human brain, such as the cerebral metabolic rate of glucose (CMRglc), regional cerebral blood flow (rCBF) and pharmacokinetic information regarding receptor-transmitter interactions such as those in the dopaminergic and histaminergic neuronal systems (Yanai & Tashiro, 2007; Tashiro, 2010). CMRglc is often measured using a radioactive analogue of glucose, [18F]fluorodeoxyglucose ([18F]FDG). In brain regions that have increased glucose consumption, an increased demand for glucose and oxygen causes dilation of cerebral capillaries, which can be measured as an increase in the regional cerebral blood flow (rCBF)(Tashiro, 2008). The rCBF is measured using radiolabeled water ([15O]H2O), though other radiation-free techniques, such as functional magnetic resonance imaging (fMRI) and near-infrared light spectroscopy (NIRS), are also available. Currently, PET is useful for visualization and quantification of various molecular phenomena, such as neurotransmission, DNA synthesis, and production of physiological and pathological proteins, in living organisms. To our knowledge, PET is one of the most sensitive imaging techniques. (Figure 1)
Information available from the human brain. Information regarding glucose and oxygen metabolism obtained using [18F]FDG PET and [15O]O2 PET. Currently, regional cerebral blood flow is measured using various methods, such as [15O]H2O PET, functional MRI (fMRI) and near infrared light spectroscopy (NIRS). Interaction of neurotransmitters and receptors is measured using PET and various radiotracers labeled with 18F and 11C nuclides.
In Japan, the incidence of cognitive disorders is increasing at an accelerated pace, partly due to the increasing size of the elderly population. Basic and clinical studies on dementia have become increasingly important. In functional neuroimaging of early Alzheimer's disease (AD), it is commonly known that a decrease in the CMRglc often starts in the posterior cingulate gyrus and propagates to the temporo-parietal and other regions, as visualized by [18F]FDG PET (Minoshima, 1994; Furukawa, 2009; Ishii, 2009). In this stage of dementia, many nerve cells are damaged and the density of healthy neurons is reduced in the gray matter, resulting in low [18F]FDG uptake. However, the regional metabolic reduction is not easily detected and is widespread during early disease stages, e.g., mild cognitive impairment (MCI)(Furukawa, 2009; Ishii, 2009). Neuronal damage is associated with high deposition of amyloid β (Aβ) protein in the brain, and massive neuronal loss is often preceded by high Aβ deposition. An early diagnosis of mild AD can be established if a tracer that specifically binds to Aβ proteins is used.
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Manabu Tashiro, Nobuyuki Okamura, Shoichi Watanuki, Shozo Furumoto, Katsutoshi Furukawa, Yoshihito Funaki, Ren Iwata, Yukitsuka Kudo, Hiroyuki Arai, Hiroshi Watabe, Kazuhiko Yanai