Littérature scientifique sur le sujet « 11C-PiB PET »

Abstract OBJECTIVE The K16ApoE peptide enhances delivery of multiple agents across the blood-brain barrier (BBB). Transgenic mouse models are central to elucidating the underlying pathophysiology of Alzheimer’s Disease (AD) and provide a system for evaluating novel therapeutic strategies. PET imaging plays a central clinical role in diagnosing human cases of AD but has had variable performance in mouse models. We investigated the role of K16ApoE to enhance delivery of a radiolabeled PET imaging tracer, 11C-PiB and assess whether this corresponds to improved PET sensitivity in APP/PS1 transgenic mice. METHODS Brain-delivery of 11C-PiB was accomplished by successive injections of K16ApoE and 11C-PiB. Distribution of 11C-PiB to the brain and heart was quantified via dynamic PET/CT imaging and digital autoradiography. RESULTS K16ApoE increased the brain uptake of 11C-PiB in both wild-type (WT) and APP/PS1 mice. Administration of K16ApoE increased the PET standard uptake value of 11C-PiB at 5 minutes in WT mice from 1.132 to 2.963 (p=0.006) and in APP/PS1 mice from 0.842 to 3.268 (p=0.016). Enhancement peaked at 5 minutes. Binding was reversible with similarly increased kinetics in both WT and APP/PS1 mice. The absolute values were higher in APP/PS1 mice suggesting increased retention. The increased retention in APP/PS1 mice was consistent with specific binding to A-beta plaques as unlabeled PiB reduced 11C-PiB signal retention. CONCLUSION K16ApoE mediates enhancement of 11C-PiB signal in APP/PS1 mice brains with increased PET sensitivity. There is increased uptake kinetics in both WT and APP/PS1 mice with specific A-beta plaque binding in the latter. This enhanced delivery of the PET tracer has implications for development and testing of new hypotheses and the efficacy of novel therapeutic paradigms. K16ApoE has potential for improving delivery of several agents across the BBB. This has implication for delivery of diagnostic and therapeutic agents for neurodegenerative and neuro-oncologic diseases.

The aim of this study was to identify the brain networks from early-phase 11C-PIB (perfusion PIB, pPIB) data and to compare the brain networks of patients with differentiating Alzheimer’s disease (AD) with cognitively normal subjects (CN) and of mild cognitively impaired patients (MCI) with CN. Forty participants (14 CN, 12 MCI, and 14 AD) underwent 11C-PIB and 18F-FDG PET/CT scans. Parallel independent component analysis (pICA) was used to identify correlated brain networks from the 11C-pPIB and 18F-FDG data, and a two-sample t-test was used to evaluate group differences in the corrected brain networks between AD and CN, and between MCI and CN. Our study identified a brain network of perfusion (early-phase 11C-PIB) that highly correlated with a glucose metabolism (18F-FDG) brain network and colocalized with the default mode network (DMN) in an AD-specific neurodegenerative cohort. Particularly, decreased 18F-FDG uptake correlated with a decreased regional cerebral blood flow in the frontal, parietal, and temporal regions of the DMN. The group comparisons revealed similar spatial patterns of the brain networks derived from the 11C-pPIB and 18F-FDG data. Our findings indicate that 11C-pPIB derived from the early-phase 11C-PIB could provide complementary information for 18F-FDG examination in AD.

ABSTRACT The complexity of the pathological reactions of the brain to an aggression caused by an internal or external noxa represents a challenge for molecular imaging. Positron emission tomography (PET) can indicate in vivo,anatomopathological changes involved in the development of different clinical symptoms in patients with neurodegenerative disorders. PET and the multitracer concept can provide information from different systems in the brain tissue building an image of the whole disease. We present here the combination of 18F-flourodeoxyglucose (FDG) and N-[11C-methyl]-L-deuterodeprenyl (DED), FDG and N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB and L-[11C]-3'4-Dihydrophenylalanine (DOPA) and finally PIB and [15O]H2O.

An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [11C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [11C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test–retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [11C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers < 1%) and reproducibility (intraclass correlation coefficient (ICC) > 0.95). [11C]PIB parametric maps were also found to be significantly correlated ( R2 > 0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [11C]PIB imaging and nonmyelin-associated proteins.

Amnestic mild cognitive impairment (aMCI) is defined as a transitional state between normal aging and Alzheimer’s disease (AD). Given the replicated finding of increased microglial activation in AD, we sought to investigate whether microglial activation is also elevated in aMCI and whether it is related to amyloid beta (Aβ) burden in-vivo . Eleven aMCI participants and 14 healthy volunteers completed positron emission tomography (PET) scans with [18F]-FEPPA and [11C]-PIB. Given the known sensitivity in affinity of second-generation TSPO radioligands, participants were genotyped for the TSPO polymorphism and only high-affinity binders were included. Dynamic [18F]-FEPPA PET images were analyzed using the 2-tissue compartment model with arterial plasma input function. Additionally, a supplementary method, the standardized uptake value ratio (SUVR), was explored. [11C]-PIB PET images were analyzed using the Logan graphical method. aMCI participants had significantly higher [11C]-PIB binding in the cortical regions. No significant differences in [18F]-FEPPA binding were observed between aMCI participants and healthy volunteers. In the aMCI group, [18F]-FEPPA and [11C]-PIB bindings were correlated in the hippocampus. There were no correlations between our PET measures and cognition. Our findings demonstrate that while Aβ burden is evident in the aMCI stage, microglial activation may not be present.

AbstractPeople with Subjective Cognitive Impairment (SCI) may be at increased risk of dementia. In this study we examined amyloid load in 5 SCI subjects and 14 controls using PIB PET scanning. One SCI subject had significantly increased PIB retention in the cortical areas of interest. Larger, longitudinal studies are indicated.

A noninvasive image-derived input function (IDIF) method using PET/MRI was applied to quantitative measurements of [11C] Pittsburgh compound-B (PiB) distribution volume (DV) and compared with other metrics. Fifty-three patients suspected of early dementia (71 ± 11 y) underwent 70 min [11C]PiB PET/MRI. Nineteen of them (68 ± 11 y) without head motion during the scan were enrolled in this study and compared with 16 age-matched healthy controls (CTL: 68 ± 11 y). The dynamic frames reconstructed from listmode PET data were used for DV calculation. IDIF with metabolite correction was applied to the Logan plot method, and DV was normalized into DV ratio (DVR) images using the cerebellar reference (DVRL). DVR and standardized uptake value ratio (SUVR) images were also calculated using the reference tissue graphical method (DVRr) and the 50–70 min static data with cerebellar reference, respectively. Cortical values were compared using the 3D-T1WI MRI segmentation. All patients were assigned to the early Alzheimer’s disease (eAD) group because of positive [11C]PiB accumulation. The correlations of regional values were better for DVRL vs. DVRr (r2 = 0.97) than for SUVR vs. DVRr (r2 = 0.88). However, all metrics clearly differentiated eAD from CTL with appropriate thresholds. Noninvasive quantitative [11C]PiB PET/MRI measurement provided equivalent DVRs with the two methods. SUVR images showed acceptable results despite inferior variability and image quality to DVR images.

The [11C]PIB PET tracer, originally developed for amyloid imaging, has been recently repurposed to quantify demyelination and remyelination in multiple sclerosis (MS). Myelin PET imaging, however, is limited by its low resolution that deteriorates the quantification accuracy of white matter (WM) lesions. Here, we introduce a novel partial volume correction (PVC) method called Multiresolution–Multimodal Resolution-Recovery (MM-RR), which uses the wavelet transform and a synergistic statistical model to exploit MRI structural images to improve the resolution of [11C]PIB PET myelin imaging. MM-RR performance was tested on a phantom acquisition and in a dataset comprising [11C]PIB PET and MR T1- and T2-weighted images of 8 healthy controls and 20 MS patients. For the control group, the MM-RR PET images showed an average increase of 5.7% in WM uptake while the grey-matter (GM) uptake remained constant, resulting in +31% WM/GM contrast. Furthermore, MM-RR PET binding maps correlated significantly with the mRNA expressions of the most represented proteins in the myelin sheath (R2 = 0.57 ± 0.09). In the patient group, MM-RR PET images showed sharper lesion contours and significant improvement in normal-appearing tissue/WM-lesion contrast compared to standard PET (contrast improvement > +40%). These results were consistent with MM-RR performances in phantom experiments.

By detecting β-amyloid ( Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (I-ICH). No previous study has directly assessed the diagnostic value of 11-Pittsburgh compound B (PiB) PET in probable CAA-related I-ICH against healthy controls (HCs). 11C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic I-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity = 91%, specificity = 55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, 11C-PiB-PET has low specificity for CAA due to the frequent occurrence of high 11C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials.

A doença de Alzheimer (DA) têm-se constituído, nos últimos anos, num sério problema de saúde pública nas sociedades ocidentais, um reflexo de uma população cada vez mais envelhecida fruto da melhoria geral da assistência médica e das mudanças demográficas daí decorrentes. Tratando-se uma doença neurodegenerativa a DA conduz à perda de diversas faculdades cognitivas e carateriza-se pela redução progressiva de tamanho e número das células cerebrais, a par da formação de emaranhados neurofibrilares (NFTs) no seu interior e placas de β-amilóide (Aβ) no espaço exterior. Na última década, o diagnóstico da DA ganhou um importante aliado com a possibilidade de realização de Tomografia por Emissão de Positrões (PET) com o radiofármaco [11C]PiB que apresenta afinidade pelas placas de Aβ. Recentemente, foi também possível aumentar a confiança deste diagnóstico complementando-o com a avaliação do metabolismo cerebral da glicose através da sua conjugação, no mesmo protocolo PET com a [18F]FDG. No que concerne à realidade portuguesa, o ICNAS, uma unidade orgânica de investigação da Universidade de Coimbra focada na Utilização Biomédica das Ciências Nucleares, que inclui na sua estrutura uma unidade de produção radiofarmacêutica com ciclotrão, é um local privilegiado para a realização de PET cerebral com [11C]PiB. Desde Abril de 2012 até Julho de 2014 foram já realizados 107 estudos com [11C]PiB, dos quais 37 fizeram parte de estudos sequenciais onde o mesmo doente realizou o estudo combinado com [11C]PiB e [18F]FDG.

Trabalho de Projeto do Mestrado Integrado em Engenharia Biomédica apresentado à Faculdade de Ciências e Tecnologia
A radioquímica e a engenharia aplicada à síntese são as fundações da produção radiofarmacêutica e o seu posterior uso em técnicas de diagnóstico por imagem como a tomografia por emissão de positrões. A introdução do [11C]iodeto de metilo e do [11C]metil triflato como moléculas marcadoras de compostos biologicamente ativos impulsionou não só o desenvolvimento de radiofármacos marcados com carbono-11 como também de soluções automatizadas para a produção destes agentes de radiomarcação.Neste trabalho, estudámos a produção automatizada de [11C]metil triflato, partindo de [11C]CO2 produzido em ciclotrão através da reação nuclear 14N(p,α)11C, através de duas vias de síntese: o tão chamado método de fase líquida e a processo em fase gasosa. A partir deste precursor radioativo, radiofármacos no estado da arte como [11C]PiB e [11C]β-CITFE podem ser produzidos, usando o método de captura de solvente, para o estudo de doenças neurodegenerativas como Alzheimer e Parkinson. Após purificação por cromatografia líquida de alta performance, estes produtos foram reformulados e esterilizados para se obter uma solução injetável pronta para uso humano, após apropriados testes de controlo de qualidade. Foi nosso objetivo avaliar qual das técnicas de síntese era mais apropriada num contexto de rotina ativa bem como otimizar o método de fase gasosa e estabelecer procedimentos de manutenção de modo a ter um equipamento funcional e fiável.Foram obtidas atividades molares de 128.65 ± 56.73 GBq/µmol e 93.39 ± 48.83 GBq/µmol e atividades de 81.24 ± 29.83 mCi e 90.66 ± 41.47 mCi no fim de síntese para [11C]PiB e [11C]β-CITFE, respetivamente. As altas atividades molares alcançadas tornam a fase gasosa a técnica de eleição para a síntese de para [11C]PiB e [11C]β-CITFE, sendo que estes resultados devem ser aplicados a outros radiofármacos marcados com carbono-11. Além disso, este processo provou ser-se muito adequado numa ativa rotina de produção pela possibilidade da realização de várias sínteses sucessivas por dia, seguido uma simples rotina diária de manutenção. As manutenções preventivas adotadas refletiram-se num processo altamente reprodutível e fiável com uma taxa de sucesso de sínteses muito elevada (aproximadamente 100%).
Radiochemistry and engineering applied to synthesis are the foundations of radiopharmaceutical production and its further use in diagnostic imaging techniques such as positron emission tomography. The introduction of [11C]methyl iodide and [11C]methyl triflate as labelling molecules of biologically active compounds motivated not only the development of carbon-11 labelled radiopharmaceuticals but also of automated solutions for the synthesis of these radiolabelling agents.In this work, we studied the automated production of [11C]methyl triflate, starting from [11C]CO2 produced in a cyclotron by the nuclear reaction 14N(p,α)11C, by two different synthetic routes: the so-called “wet” method and the gas phase approach. From this radioactive precursor, state-of-the-art radiopharmaceuticals such as [11C]PiB and [11C]β-CITFE can be produced, using the captive solvent method, to study important neurodegenerative diseases such as Alzheimer’s and Parkinson’s. After purification using high performance liquid chromatography, these products were reformulated and sterilized to obtain an injectable solution ready for human use after the appropriate quality control tests. It was our goal to evaluate which of the synthesis techniques was more suitable in the routine context as well as to optimise the gas phase approach and establish maintenance procedures in order to have a functional and reliable equipment.Molar activities of 128.65 ± 56.73 GBq/µmol and 93.39 ± 48.83 GBq/µmol, and 81.24 ± 29.83 mCi and 90.66 ± 41.47 mCi activities were obtained in the end of synthesis for [11C]PiB and [11C]β-CITFE, respectively. High molar activities attained make the gas phase the technique of choice for [11C]PiB and [11C]β-CITFE synthesis and these results should be applicable to other 11C-radiopharmaceuticals. Additionally, this process proved to be very suitable in a busy production schedule due to the possibility of performing multiple synthesis per day following a very simple daily maintenance routine. The established preventive maintenance procedures have resulted in a highly reproducible and reliable process with a very high synthesis success rate (approximately 100%).

Trabalho de Projeto do Mestrado Integrado em Engenharia Biomédica apresentado à Faculdade de Ciências e Tecnologia
A doença de Alzheimer (AD) é a doença neurodegenerativa responsável pelo maior número de casos de demência. Tomografia por emissão de positrões (PET) com 11C-Pittsburgh Compound B (PiB) e 11C-(R)-PK11195 (PK) são duas modalidades utilizadas na visualização das placas amilóides e da microglia ativada no cérebro humano, respetivamente. Uma vez que as placas amilóides são o principal identificador da AD e que a microglia ativada é também recorrentemente encontrada no cérebro dos doentes de Alzheimer, estes representam dois potenciais biomarcadores imagiológicos que podem ser usados como ferramenta de diagnóstico precoce da doença. Este trabalho teve como objetivo principal a resolução de um problema de classificação binário, entre controlos saudáveis (HC) e pacientes de Alzheimer, através de métodos de machine learning (ML) baseados em dois traçadores imagiológicos de PET: o PiB e o PK. Outro objetivo deste trabalho, incluiu a identificação das regiões cerebrais onde o PiB e o PK apresentam maior correlação, quer a nível do voxel quer a nível regional. O dataset deste estudo, que incluiu 41 indivíduos (20 doentes de Alzheimer e 21 HC), foi dividido em três grupos por forma a melhor compreender o impacto do intervalo de tempo considerado no protocolo de aquisição da PET. O grupo TOT, composto pelas imagens PET adquiridas durante o tempo total de biodistribuição do PiB, e os grupos 4070 e 4060, compostos por imagens PET adquiridas durante o intervalo de tempo caraterístico de acumulação de cada um destes radiofármacos. Após quantificação, pré-processamento, extração e seleção das features, as features selecionadas das imagens PET, com PiB e com PK, foram utilizadas como variáveis preditoras em classificadores baseados em support vector machines (SVM). Para estudar o impacto das diferentes regiões de referência utilizadas na normalização de imagens PET com PK, e a influência do método de quantificação escolhido, os grupos de AD e HC de diferentes formas de quantificação de imagens PET com PK foram comparados a nível do voxel. Adicionalmente, calculou-se para diferentes regiões cerebrais a correlação existente entre imagens PET com PiB em termos da taxa do valor de captação padronizado (SUVr) e as imagens PET com diferentes formas de quantificação PK.O classificador com o melhor desempenho foi construído com features extraídas de imagens PET com PiB do grupo 4070 normalizadas pelo cerebelo (exatidão – 0.925, sensibilidade-1.000, especificidade-0.857). Por conseguinte, para imagens PET com PiB, o cerebelo foi a região cerebral onde a diferença na acumulação de amilóides entre os grupos de AD e HC foi a menos significativa, isto é, foi a melhor região de referência. De referir que quando o cerebelo é utilizado como região de referência em imagens PET com PiB, é verificada uma maior correlação a nível regional para com as imagens PET com PK, comparativamente à normalização realizada através da matéria branca. As features extraídas a nível regional de imagens PET com PK não melhoraram nem a exatidão nem a sensibilidade do classificador apenas baseado em features extraídas de imagens PET com PiB. A correlação a nível regional entre imagens PET com PiB e com PK sugere que o cerebelo apresenta uma ligação específica ao PK; consequentemente, o método supervised cluster analysis algorithm based on four kinetic classes (SVCA4) relevou ser a melhor abordagem para a normalização de imagens PET com PK. As duas formas de quantificação de imagens PET com PK apresentaram diferenças muito pouco significativas entre os grupos AD e HC a nível do voxel, o que sugere que a biodistribuição do PK no cérebro não permite diferenciar grupos. Esta afirmação apoia a associação que se tem vindo a estabelecer entre a microglia ativada e a neuroinflamação. Como a neuroinflamação é característica de cada indivíduo, isto é, é aleatoriamente distribuída no cérebro dos doentes de Alzheimer, o esperado é a não diferenciação de grupos por parte do PK. Foram encontradas cinco regiões cerebrais onde a correlação a nível do voxel se relevou elevada para quase todas as regiões de referência consideradas, córtex motor primário, córtex visual primário, córtex de associação somatossensorial, córtex visual associativo e córtex pré-motor. Tanto o precuneus (P) como o lóbulo parietal inferior (PI) desempenham funções importantes no processamento visual e espacial. Por conseguinte, é natural que os resultados da correlação a nível regional estejam associados com os obtidos a nível do voxel.Em suma, de acordo com o estudo realizado, o classificador construído apenas com features extraídas de imagens PET com PiB do grupo 4070, usando o cerebelo como região de referência, foi o classificador que apresentou uma melhor resposta ao problema proposto, classificação binária de indivíduos como AD ou HC. Adicionalmente, também foi descoberta uma correlação positiva entre o PK e o PiB em regiões cerebrais responsáveis pela função motora e pelo processamento visual.
Alzheimer’s disease (AD) is one of the main neurodegenerative disorders causing dementia. Positron emission tomography (PET) neuroimaging with 11C-Pittsburgh Compound B (PiB) and 11C-(R)-PK11195 (PK) are two of the existing modalities to assess amyloid plaque and activated microglia in human brain, respectively. Since amyloid plaque is the main hallmark of AD and activated microglia is currently found in the brain of AD patients, these imaging biomarkers can be used in diagnostic workup and to achieve early AD diagnosis.The main goal of the present study is to solve a binary classification problem between healthy controls (HC) and AD patients, by using machine learning (ML) methods based on two PET imaging biomarkers, PiB and PK. Another important goal of this work includes the identification of the brain regions where PiB and PK are most correlated, at both regional and voxel level.In the present study it was included 41 subjects (20 AD and 21 HC). To understand the impact of the time interval considered in PET image acquisition, the dataset was split in three different groups. Group TOT composed by PiB PET images acquired during the total time of PiB biodistribution, and groups 4070 and 4060, acquired during the characteristic accumulation time of PiB and PK, between minute 40 and 70, and 40 and 60, after administration, respectively. After quantification, pre-processing, feature extraction and selection, PiB and PK PET images were submitted to classification using a support vector machines (SVM) approach. Voxel-wise comparison between AD and HC groups of different quantified PK PET images were performed to understand the impact of distinct reference regions in the normalization of PK PET images and the influence of the quantification method used. Also, voxel-wise and region of interest (ROI) based correlation between standard uptake value ratio (SUVr) PiB and different quantified PK PET images were calculated.Normalization by cerebellum of PiB PET images of group 4070 yielded the best classification accuracy of AD (accuracy-0.925, sensitivity-1.000, specificity-0.857). Thus, for PiB PET images, cerebellum appears to be the brain region where amyloid accumulation bears the least significant differences between HC and AD patients, i.e., the best reference region to do the normalization. Also, when using the cerebellum as reference region of PiB PET images, stronger ROI-based correlation with binding potential (BP) PK PET images in several brain regions was found, compared to normalization based on white matter. Features extracted at regional level from PK PET images did not show improvement, neither in accuracy nor in sensitivity, of the classifier only based on features extracted from PiB PET images. ROI-based correlation results suggest specific binding of PK to cerebellum; thus, supervised cluster analysis algorithm based on four kinetic classes (SVCA4) showed to be the best approach to do the normalization of PK PET images. Both types of quantified PK PET images did not show significant differences between groups at voxel level. This suggests that PK biodistribution in the brain is not relevant for group differentiation. The reason why is probably related to the fact that activated microglia is associated with neuroinflammation, and this process is quite variable across participants, i.e., it is randomly distributed across brains of AD patients. There were five brain regions where the correlation at voxel level between PK and SUVr PiB PET images agreed the most for all reference regions considered, primary motor cortex, primary visual cortex, somatosensory association cortex, associative visual cortex and premotor cortex. Since, both precuneus (P) and parietal inferior (PI) have important roles in visuospatial processing, ROI-based correlation results are consistent with the ones obtained at voxel level.Overall, according with the present study, the classifier only based on features extracted from PiB PET images of group 4070, using cerebellum as reference region, was the classifier who solved more accurately the problem proposed, binary classification in AD. Additionally it was also found a positive correlation between PK and PiB in particular in brain regions responsible for motor function and visual processing.
FCT

碩士
國立陽明大學
生物醫學影像暨放射科學系
101
Objectives: Alzheimer’ disease (AD) is typified by deposition of β-amyloid (Aβ) within the brain accompany with cognitive decline. Imaging Aβ plaque could be useful for the development of the therapeutic and diagnosis target in AD. In this study, we aimed to access the change of Aβ and neuronal metabolism in the brain in J20 AD mice over age by using [11C]PIB and [18F]FDG PET. Methods: The human amyloid precursor protein (hAPP) transgenic mouse lines J20 were bred and reared in our colony; littermates without hAPP were used as wild-type (wt) mice. The behavior test was applied to evaluate the change of memory and learning in APP mice. The animals (N=6/group) were imaged monthly from month 4 to month 12. The 20 min static imaging were performed after i.v. injection of [11C]PIB or [18F]FDG at 30 min. Thereafter, the brains of animals were removed for immunehistochemical staining for Aβ. Results: The memory and learning performance was significantly deficit in APP mice after 5-6 months. The accumulation of [11C]PIB tended higher in APP mice than the that of wt mice since month 5. The age-dependent increased accumulation of [11C]PIB in APP mice appeared from month 5 to month 12. No significant difference of [18F]FDG uptake was observed between APP and wt mice in whole study period. Conclusions: [11C]PIB PET could be used to distinguish APP mice from the control ones before onset at month 5 when pathological change of Aβ in hippocampus appears. Due to the limitation of micro PET imaging, the subtle change in the brain in earlier stage (