| ENGLISH ABSTRACTPart?The research of Beta amyloid imaging with domestic 11C-PIB and evaluation the efficiency in clinical utilitiesPurpose:Based on the former chemical synthesis module, we investigated the automated synthesis of AD amyloid imaging agent [11C]6-OH-BTA-1 (11C-PIB), aimed at completely domestic produce of PIB and its precursor. In addition, we took quality control of PIB and verified the clinical efficacy of drugs by the clinical applications. Material and methods:Turn 11C-iodo methane (11CH3I) deoxidized from lithium aluminum hydride/THF (LAH/THF) ion into 11C-trifluoro-methanesulfonate (11CH3OTf) with higher activity, then introduced into conical reaction flask with PIB precursor (6-OH-BTA-O, imported and home-made precursors) inside. Reaction is on ice-salt conditions in butanone solution. Then employed the improved HPLC to purify the products, and took quality control finally. Biological characteristics and safety of the self-produced PIB precursors and the import ones were compared; Groups of subjects took brain PET imaging to verify the feasibility of self-produced PIB, image quality and adverse reactions after injection were assessed. Results:With the improved automatic produce process,11C-PIB in 10% ethanol solution available for injection was ultimately produced, which is completely free of acetonitrile. Physical, chemical, biological qualities of 11C-PIB were consistent with SFDA issued "positron radiopharmaceutical quality control guidelines". Relative to the produce amount of imported precursor (1mg), Self-produced precursor (6-8mg) needed a larger amount, but the price is relatively cheaper, while the success rate of synthesis, the radiochemical yield, radiochemical purity, production rate were similar. Except distinctive pain occur after injection (with a small amount of ethanol solution), no other adverse reactions observed. Brain PET imaging with agent self-produced PIB showed high quality and the distribution of radioactivity were consistent with former literature. No significant difference was noticed in the curve of time-global activity between self-produced and imported PIB. Conclusions:The self-produced precursors of 11C-PIB production route is stable and safe for human brain imaging, which support proof of feasibility of self production of PIB and its precursor. Key words:Positron emission tomography; quality control; [N-methyl-11C]2-[4'-(methylamino)phenyl]-6-hydroxyphenylbenzothiazole CLC number:R817.4Part IIResearch of FDG PET in Alzheimer's disease and mild cognitive impairment using Statistical Parametric MappingPurpose:Voxel-based analysis of the regional cerebral glucose metabolism in patients with mild Alzheimer's disease (AD), amnestic-type mild cognitive impairment (aMCI) compared to normal aging as control associated with characteristic and progressive reductions with Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET).Material and Methods:Twenty-seven patients with mild AD patients,10 aMCI patients and 21 age-matched normal aging were enrolled in this study. Glucose metabolism differences of brain were assessed by Statistical Parametric Mapping 8 (SPM8) based on the Matlab platform to compare the normal aging with the cognitive declined. Results:In comparison with the normal aging group, the AD group had significantly lower brain glucose metabolism in posterior cingulate (BA23,31), precuneus (BA19), bilateral parietal (BA40), bilateral temporal lobe (BA20,21,22,37) and bilateral frontal cortex (BA6,9,10) (p<0.001, uncorrected, K?50 voxels). Compared with the aMCI group, the AD group had hypometabolism in posterior cingulate (BA23, 31), precuneus (BA19), temporal lobe (BA40,20,21,22,39) and frontal cortex (BA6,8,9) (p<0.001, uncorrected, K?50 voxels). Decreased voxels of glucose metabolism between the AD group and the aMCI group were less than those between the AD group and the normal aging group. Brain glucose metabolism in aMCI group compared to the normal aging group decreased only in the right occipital cortex (BA17) (p<0.05, uncorrected). Conclusion: Voxel-wise comparison of glucose metabolism in whole brain between the patients and the normal aging can reveal widespread hypomeabolism in mild Alzheimer's disease. However aMCI had less metabolism reduction than the normal aging.Part IIIThe research of 11C-PIB amyloid imaging combined with 18F-FDG PET in normal aging and cognitive declinedObjective:Beta amyloid plaques and impaired glucose metabolism are the most prevalent pathological characteristics of Alzheimer's disease (AD). The aim was to reveal the characteristics of positron emission tomography (PET) imaging using radiotracers (11)C-Pittsburgh compound B (PIB) in normal aging and the cognitive declined combined with fluoro-deoxyglucose (FDG) PET.Material and Methods:Six normal aging,6 aMCI patients,13 mild AD patients and 3 other cognitive declined patients were enrolled in this study. The normal aging and the cognitive declined was compared by the distribution of PIB in the whole brain. It was assessed by visual analysis, regional of interest (ROI) analysis and Statistical Parametric Mapping 8 (SPM8) based on the Matlab platform. Results:The distribution of PIB showed rapid blood flow in early phase and then washed out quickly especially in cerebellum in all subjects. The type of distribution was different 40 minutes later after injection in AD and the normal aging. PIB retention was high in frontal, lateral temporal lobe, posterior cingulate and precuneus in the AD and four aMCI. Only little PIB was distributed in white matter and pons in the normal aging. The sensitivity of PIB was 100% while FDG was 84.6% in AD; PIB was negative in progressive supranuclear palsy, frontotemporal dementia and vascular dementia while FDG had changes. Compared with the normal aging, frontal, lateral temporal lobe, parietal lobe, cingulate, precuneus, and basal ganglia increased in AD and MCI(p<0.001, uncorrected, K?50 pixels). No difference was found in medial temporal lobe. The curve of SUVR increased in AD while decreased in the normal aging from 40 to 60 minutes. Conclusions:The amount of PIB retention was different in AD other than the normal aging after 40 minutes post-injection which can diagnose and differentiate the different types of cognitive dysfunction. The SUV Ratio curve rase after 40 minutes which tested the feasibility of PIB in diagnosis of AD. The distribution of PIB was positive in all subjects. But 4 AD-like MCI patients were negative with glucose metabolism. Based on the above, we can conclude that PIB might be useful in the early stage of possible AD (aMCI). |
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