Beta-Amyloid PET Imaging Of AD Diagnosis And Therapeutic Effect Monitoring

Objective1 Preparation of¹¹C-PIB and 4'-Schiff-O[¹¹C]CH₃ as Aβamyloid imaging agent,determine the affinity to Aβ1-40.2 determine the localization and load of APs in the brains of AD patients using beta amyloid PET imaging,and to evaluate the value of PET imaging in prognosis of MCI in vivo.3 investigate the value of PET imaging in the preparation of Alzheimer's disease rat model and the value of evaluation of therapeutic effect of FZS by PET imaging.Methods1 The mice with ¹¹C-PIB or 4'-Schiff-O[¹¹C]CH₃injection were sacrificed, taken out brain and others tissue,weighted tissue and radiocounted.Aβ1-40 injection rat and control rats underwent ¹¹C-PIB or 4'-Schiff-O[¹¹C]CH3 PET study. The sections of the brain tissues for both contral rat and AD model were stained with HE method and congo red.2 21 subjects were divided into three groups:6 AD patients,8 MCI patients and 7 normal control(HC)subjects.Sequential emission scans were obtained after 11C-PIB administration..The PET results were analyzed with visual and region of interest(ROI)method;calculate the ratio of radioactivity clearance of interested brain regions from 5 rain to 45 min after ¹¹C-PIB administration,and the ratio of brain region to cerebellum.3 aged AD rat models and control rats underwent FZS treatment and ¹⁸F-FDG and ¹¹C-PIB PET studies.The sections of the brain tissues for both contral rat and aged AD model were stained with HE method,congo red,Aβ immunofluorescence,Brdu immunofluorescence and Neun immunofluorescence.Results1 The greater accumulation and rapid clearance of ¹¹C-PIB or 4'-Schiff-O[¹¹C]CH₃ was observed in mice brain,the two tracers has high affinity to Aβ1-40, crossed the blood-brain barrier very rapidly,and cleared rapidly from healthy brain.2 Visual and region of interest(ROI)method found that AD patients typically showed marked retention of ¹¹C-PIB in related cortex where large amount of amyloid deposited.In MCI patients,the PET image of some patients are HC-like,and others are AD-like.3 4'-Schiff-O[¹¹C]CH₃ bound to Aβ(1-40)fibrils exhibited an good affinity in vivo and in vitro.4'-Schiff-O[11C]CH3 is a promising tracer for amyloid protein imaging.4 Diffuse neuronal loss and Aβdeposition can be detected in the hippocampus and cortex in the aged AD rats,FZS can improve the glucose metabolism,but can not improve the amyloid deposition in aged AD rats. immunofluorescence indicates that FZS leads to the the neuronal proliferation.Conclusion1 ¹¹C-PIB and 4'-Schiff-O[¹¹C]CH3 are promising tracers for AD imaging and have good affinity to Aβ.2 Aβimaging are promising in providing reliable quantitative information on APs in living AD patients and in evaluating the prognosis of MCI.3 PET imaging,combinding with the behavioral observation,can be on of standards of verifying the AD rat model,and PET imaging can be a method to valuation of therapeutic effect.FZS ameliorates memory dysfunction of the aged rats is at least parcially via the enhancement of the neuronal proliferation and survive.