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In a Japanese nationwide survey on the use of FDG-PET for dementia, a total of 406 cases acquired during the period from April 2001 to March 2002 were collected from 15 PET centers. The purpose of the PET scans included (A) diagnosis of patients with memory disturbance for possible early stage of Alzheimer's disease (154 cases) and (B) differential diagnosis for dementia-related neurodegenerative diseases (144 cases), and the PET achieved the purpose in most cases. Based on the survey, an economic evaluation was performed on the 2-year projected cost and benefit of treating patients with donepezil that are diagnosed as Alzheimer's disease with FDG-PET. The estimation indicated that early and/or accurate diagnosis of Alzheimer's disease with FDG-PET followed by initiation of the donepezil treatment would delay the disease progress and reduce the care cost more than it would increase the cost by the PET and the drug therapy. The average reduction of the total cost was estimated to be ¥61 500 (A) and ¥13 700 (B) per person. The increase of the quality adjusted life year (QALY) was predicted to be 0.044 (A) and 0.014 (B). Therefore, incorporation of PET into the clinical path was shown to be economically dominant. [Copyright &y& Elsevier]

Background: Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings. Here, we aimed to examined the differences in TSPO binding and CB2 availability at an early stage of stroke in the same animal using positron emission tomography (PET).Methods: We used a total of eight Sprague-Dawley rats that underwent photothrombotic stroke surgery. The binding levels of a TSPO tracer [11C](R)PK11195 and a CB2 tracer [11C]NE40 were measured at 24 h after the surgery in the same animal using PET in combination with immunohistochemistry for CB2 and several other markers. A morphological inspection was also performed with X-ray computed tomography for small animals.Results: The levels of [11C]NE40 binding potential (BPND) were significantly higher in the cerebral cortical region on the lesion side than those on the non-lesion side, whereas no difference was found in the levels of [11C](R)PK11195 BPND between hemispheres. The tracer influx index (R1) data were all reduced on the lesion side irrespective of tracers. This increase in [11C]NE40 BPND was concomitant with an elevation in CB2 expression mainly within the microglia in the peri-infarct area, as shown by immunohistochemical examinations with Iba-1, CD11b/c+, and NG2+ staining.Conclusions: The present results provide in vivo evidence of different responses of microglia occurring in the acute state of stroke. The use of the CB2 tracer [11C]NE40 allows us to evaluate the roles played by the neuroprotective aspect of microglia in acute neuroinflammatory processes. [ABSTRACT FROM AUTHOR]

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C](R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer’s disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C](R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C](R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C](R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration. [ABSTRACT FROM AUTHOR]

Purpose Amyloid β protein (Aβ) is known as a pathological substance in Alzheimer’s disease (AD) and is assumed to coexist with a degree of activated microglia in the brain. However, it remains unclear whether these two events occur in parallel with characteristic hypometabolism in AD in vivo. The purpose of the present study was to clarify the in vivo relationship between Aβ accumulation and neuroinflammation in those specific brain regions in early AD. Methods Eleven nootropic drug-naïve AD patients underwent a series of positron emission tomography (PET) measurements with [11C](R)PK11195, [11C]PIB and [18F]FDG and a battery of cognitive tests within the same day. The binding potentials (BPs) of [11C](R)PK11195 were directly compared with those of [11C]PIB in the brain regions with reduced glucose metabolism. Results BPs of [11C](R)PK11195 and [11C]PIB were significantly higher in the parietotemporal regions of AD patients than in ten healthy controls. In AD patients, there was a negative correlation between dementia score and [11C](R)PK11195 BPs, but not [11C]PIB, in the limbic, precuneus and prefrontal regions. Direct comparisons showed a significant negative correlation between [11C](R)PK11195 and [11C]PIB BPs in the posterior cingulate cortex (PCC) (p < 0.05, corrected) that manifested the most severe reduction in [18F]FDG uptake. Conclusion A lack of coupling between microglial activation and amyloid deposits may indicate that Aβ accumulation shown by [11C]PIB is not always the primary cause of microglial activation, but rather the negative correlation present in the PCC suggests that microglia can show higher activation during the production of Aβ in early AD. [ABSTRACT FROM AUTHOR]

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C15O2) or 15O-labelled water (H215O), 15O-labelled carbon monoxide (C15O) and 15O-labelled oxygen (15O2) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of 15O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C15O2 (or H215O) and 15O2. All used C15O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml-1 min-1; CBV=3.8±0.7 ml 100 ml-1; OEF=0.44±0.06; CMRO2=3.3±0.5 ml 100 ml-1 min-1. Significant between-centre variation was observed in CBV, OEF and CMRO2 by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO2 was acceptably small. Building a database of normal cerebral haemodynamics obtained by the15O-PET methods may be practicable. [ABSTRACT FROM AUTHOR]