Background: Performing aerobic exercise and maintaining high levels of aerobic fitness may have positive effects on both brain structure and function in older adults. Despite decades of research however, there is still a rather poor understanding of the neurocognitive mechanisms explaining the positive effects of aerobic exercise on cognition. Changes in prefrontal gray matter as well as dopaminergic neurotransmission in striatum are both candidate neurocognitive mechanisms. The main aims of this thesis are: 1. To investigate the effects of aerobic exercise and fitness on cognition and magnetic resonance imaging (MRI) derived gray matter volumes using data from a 6 month physical exercise intervention in older adults (Study I). 2. To simulate the effect of atrophy in longitudinal positron emission tomography (PET) which could pose a challenge to interpreting changes in longitudinal PET imaging (Study II). 3. To study the influence of aerobic exercise and fitness on the dopamine D2-receptor (D2R) system in striatum using [11C]raclopride PET as a potential mechanism for improved cognition (Study III). Results: In Study I, aerobic exercise was found to improve cognitive performance in a broad, rather than domain-specific sense. Moreover, aerobic fitness was related to prefrontal cortical thickness, and improved aerobic fitness over 6 months was related to increased hippocampal volume. In Study II, we identified areas in the striatum vulnerable to the effect of shrinkage, which should be considered in longitudinal PET imaging. Finally, in Study III, the effect of being aerobically fit, and improving fitness levels was found to impact dopaminergic neurotransmission in the striatum, which in turn mediated fitness-induced improvements in working memory updating performance. Conclusion: The findings in this thesis provide novel evidence regarding the neurocognitive mechanisms of aerobic exercise-induced improvements in cognition, and impacts the interpretation of longitudinal PET imaging. Performing aerobic exercise and staying aerobically fit at an older age have positive effects on cognition and brain systems important for memory and cognition. Specifically, fitness-induced changes to the dopaminergic system stands out as one novel neurocognitive mechanism explaining the positive effects of aerobic fitness on working-memory performance in healthy older adults.

Non invasive in vivo imaging will lead to better understanding of Angiotensin II Type 1 Receptor’s (AT1R) role in disease progression and may guide therapy in cardiovascular patients. Two models were used in this project: 5/6 nephrectomy and transient left anterior descending (LAD) ligation. Rats were scanned with [13N]ammonia and [11C]methyl-candesartan, both of which are Positron Emission Tomography (PET) tracers, at 8 weeks (nephrectomy) and 2 weeks (LAD ligation) after surgery. Western blot analysis was used to corroborate PET data. Nephrectomy: Renal AT1R image analysis displayed a 40% decrease in kidney AT1R in nephrectomized animals compared to sham (p<0.05) which was confirmed with Western blot and biodistribution. LAD ligation: Left Ventricle AT1R Western blot analysis exhibited a 60% increase in 20min ligation (p<0.05) with maintained myocardial blood flow. In conclusion, changes in renal AT1R were successfully imaged using [11C]methyl-candesartan in nephrectomized animals, and 20min LAD ligation/reperfusion is an appropriate model to image an increase in cardiac AT1R following ischemic injury.

Ce mémoire présente mes travaux ayant menés au développement d’une première génération de radioligands marqués au fluor-18 (t1/2 = 110 min) et au carbone-11 (t1/2 = 20.4 min) destinés à l’imagerie cérébrale in vivo du récepteur tyrosine kinase neurotrophique de type 2 (TrkB) en tomographie par émission de positons (TEP). Ces travaux reposent sur l’identification récente de ligands de TrkB non peptidiques à hautes affinités dérivés du 7,8-dihydroxyflavone. La synthèse d’une série de dérivés du 7,8-dihydroxyflavone non-radioactifs de même que des précuseurs à l’incorporation du fluro-18 et du carbone-11 a d’abord été effectuée. Partant des précurseurs adéquats synthétisés, la radiosynthèse de deux radioligands, l’un marqué au fluor-18 et l’autre au carbone-11, a été développée. Ces radiosynthèses reposent respectivement sur une 18F-radiofluorination nucléophile aromatique nouvelle et hautement efficace et sur une 11C-méthylation N-sélective. Les radiotraceurs de TrkB ainsi obtenus ont ensuite été évalués in vitro en autoradiographie et in vivo en tant que traceurs TEP dans des rats. L’évaluation des propriétés physico-chimique de même que de la stabilité in vitro des radiotraceurs sont présentées. Partant d’une série d’analogues cristallisés de ces flavones synthétiques, une étude de relation structure-activité a été menée. La combinaison de cette étude, de pair avec l’évaluation in vivo de la première génération de radiotraceurs de TrkB a aussi permis d’investiguer les pharmacophores nécessaires à l’affinité de ces ligands de même que d’identifier des fragments structurels associés au métabolisme des radiotraceurs. La radiosynthèse d’un troisième radioligand de TrkB et son évaluation TEP in vivo de même que la mise en lumière des modifications structurelles utiles au développement d’une seconde génération de radioligands de TrkB avec des propriétés optimisées pour fin d’imagerie TEP sont aussi détaillés. / This thesis describes my contribution leading to the development of the first-generation positron emission tomography (PET) radioligands labeled with fluorine-18 (t1/2 = 110 min) or carbon-11 (t1/2 = 20.4 min) for the in vivo brain imaging of tropomyosin-related kinase B (TrkB). This research follows from the recent discovery of non-peptidic, high-affinity TrkB ligands derived from 7,8-dihydroxyflavone. The synthesis of non-radioactive 7,8-dihydroxyflavone derivatives and radiolabeling precursors amenable to fluorine-18 and carbon-11 incorporation was performed. Two synthesized compounds have been brought forward as precursors for radiolabeling with either fluorine-18 or carbon-11. Radiosynthesis involved either a novel nucleophilic aromatic subsitution with [18F]fluoride, or N-methylation with [11C]methyl iodide or [11C] methyl triflate. The resulting radiotracers were assessed in vitro by autoradiography and in vivo by PET scans of rats. The physicochemical properties and serum stability of these tracers were also evaluated. X-ray crystal structures of a series of synthetic flavone analogues were used as basis for structure-activity relationship (SAR) analysis. In combination with the above in vivo PET evaluation of these compounds, certain pharmacophores were shown essential for ligand binding affinity. In addition, some structural fragments were associated with in vivo ligand metabolism. The development and radiosynthesis of a third TrkB radiotracer, along with its in vivo PET evaluation and structural analysis, is also described here. In all, better understanding of these tracers have led to the design of potential second-generation TrkB ligands with more optimal properties as PET radiotracers.

Ce mémoire présente mes travaux ayant menés au développement d’une première génération de radioligands marqués au fluor-18 (t1/2 = 110 min) et au carbone-11 (t1/2 = 20.4 min) destinés à l’imagerie cérébrale in vivo du récepteur tyrosine kinase neurotrophique de type 2 (TrkB) en tomographie par émission de positons (TEP). Ces travaux reposent sur l’identification récente de ligands de TrkB non peptidiques à hautes affinités dérivés du 7,8-dihydroxyflavone. La synthèse d’une série de dérivés du 7,8-dihydroxyflavone non-radioactifs de même que des précuseurs à l’incorporation du fluro-18 et du carbone-11 a d’abord été effectuée. Partant des précurseurs adéquats synthétisés, la radiosynthèse de deux radioligands, l’un marqué au fluor-18 et l’autre au carbone-11, a été développée. Ces radiosynthèses reposent respectivement sur une 18F-radiofluorination nucléophile aromatique nouvelle et hautement efficace et sur une 11C-méthylation N-sélective. Les radiotraceurs de TrkB ainsi obtenus ont ensuite été évalués in vitro en autoradiographie et in vivo en tant que traceurs TEP dans des rats. L’évaluation des propriétés physico-chimique de même que de la stabilité in vitro des radiotraceurs sont présentées. Partant d’une série d’analogues cristallisés de ces flavones synthétiques, une étude de relation structure-activité a été menée. La combinaison de cette étude, de pair avec l’évaluation in vivo de la première génération de radiotraceurs de TrkB a aussi permis d’investiguer les pharmacophores nécessaires à l’affinité de ces ligands de même que d’identifier des fragments structurels associés au métabolisme des radiotraceurs. La radiosynthèse d’un troisième radioligand de TrkB et son évaluation TEP in vivo de même que la mise en lumière des modifications structurelles utiles au développement d’une seconde génération de radioligands de TrkB avec des propriétés optimisées pour fin d’imagerie TEP sont aussi détaillés. / This thesis describes my contribution leading to the development of the first-generation positron emission tomography (PET) radioligands labeled with fluorine-18 (t1/2 = 110 min) or carbon-11 (t1/2 = 20.4 min) for the in vivo brain imaging of tropomyosin-related kinase B (TrkB). This research follows from the recent discovery of non-peptidic, high-affinity TrkB ligands derived from 7,8-dihydroxyflavone. The synthesis of non-radioactive 7,8-dihydroxyflavone derivatives and radiolabeling precursors amenable to fluorine-18 and carbon-11 incorporation was performed. Two synthesized compounds have been brought forward as precursors for radiolabeling with either fluorine-18 or carbon-11. Radiosynthesis involved either a novel nucleophilic aromatic subsitution with [18F]fluoride, or N-methylation with [11C]methyl iodide or [11C] methyl triflate. The resulting radiotracers were assessed in vitro by autoradiography and in vivo by PET scans of rats. The physicochemical properties and serum stability of these tracers were also evaluated. X-ray crystal structures of a series of synthetic flavone analogues were used as basis for structure-activity relationship (SAR) analysis. In combination with the above in vivo PET evaluation of these compounds, certain pharmacophores were shown essential for ligand binding affinity. In addition, some structural fragments were associated with in vivo ligand metabolism. The development and radiosynthesis of a third TrkB radiotracer, along with its in vivo PET evaluation and structural analysis, is also described here. In all, better understanding of these tracers have led to the design of potential second-generation TrkB ligands with more optimal properties as PET radiotracers.

<p>An <i>in vitro</i> method was developed for measuring aromatase, based on binding of competitive aromatase inhibitor [¹¹C]vorozole to the active site of the enzyme. [¹¹C]Vorozole displayed high, specific binding <i>in vitro</i> to human placenta and human granulosa cells (GC), both fresh and frozen/thawed cells, provided correct procedures were used. High, specific binding was also observed in pig and rat ovaries, whereas binding in other tissues was unspecific and usually low. Aromatase concentrations measured by [¹¹C]vorozole binding correlated well to aromatase activity measured by [³H]water release from 1β[³H]androstenedione. </p><p>In human GC <i>in vitro</i>, low concentrations of 5α-dihydrotestosterone (DHT), but not of other androgens, stimulated aromatase activity measured by [³H]water release but had no effects on aromatase concentration measured by [¹¹C]vorozole binding. DHT may interact with aromatase differently than other androgens, perhaps by changing aromatase affinity to precursor. </p><p>In the rat estrous cycle, aromatase activity in ovarian homogenate, measured by [³H]water release, together with serum androstenedione and estradiol-17β, peaked between 6 and 13 h after onset of the light period of proestrus, the former activity being independent of radioactive substrate concentration. [¹¹C]Vorozole binding characteristics changed more rapidly than <i>de novo</i> synthesis of the enzyme. [¹¹C]Vorozole binding K_dshowed close inverse correlation to aromatase activity in ovarian homogenate and to serum estradiol-17β. Rapid changes in substrate affinity rather than changes in substrate concentration or <i>de novo</i> synthesis of the enzyme may thus be important for regulation of ovarian aromatase. </p><p>The [¹¹C]vorozole <i>in vivo</i> technique yields additional information compared with traditional in vitro techniques. </p>

<p>One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter ¹¹C (t_½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [¹¹C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [¹¹C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and ¹H and ¹³C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed.</p><p>[<i>carbonyl-</i>¹¹C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [<i>carboxyl-</i>¹¹C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [<i>carbonyl-</i>¹¹C]Esters were synthesized using primary and secondary alcohols, <i>tert-</i>butanol, and phenol. Bases were KOH, BuLi, LiHDMS.</p><p>The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases.</p><p>A mild procedure for the ¹¹C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide.</p><p>Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [<i>carbonyl</i>-¹¹C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps.</p><p>In addition, several (¹³C)compounds were synthesised using the described methods.</p><p>Free radical carbonylation may be used for the ¹¹C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.</p>

An in vitro method was developed for measuring aromatase, based on binding of competitive aromatase inhibitor [11C]vorozole to the active site of the enzyme. [11C]Vorozole displayed high, specific binding in vitro to human placenta and human granulosa cells (GC), both fresh and frozen/thawed cells, provided correct procedures were used. High, specific binding was also observed in pig and rat ovaries, whereas binding in other tissues was unspecific and usually low. Aromatase concentrations measured by [11C]vorozole binding correlated well to aromatase activity measured by [3H]water release from 1β[3H]androstenedione. In human GC in vitro, low concentrations of 5α-dihydrotestosterone (DHT), but not of other androgens, stimulated aromatase activity measured by [3H]water release but had no effects on aromatase concentration measured by [11C]vorozole binding. DHT may interact with aromatase differently than other androgens, perhaps by changing aromatase affinity to precursor. In the rat estrous cycle, aromatase activity in ovarian homogenate, measured by [3H]water release, together with serum androstenedione and estradiol-17β, peaked between 6 and 13 h after onset of the light period of proestrus, the former activity being independent of radioactive substrate concentration. [11C]Vorozole binding characteristics changed more rapidly than de novo synthesis of the enzyme. [11C]Vorozole binding Kd showed close inverse correlation to aromatase activity in ovarian homogenate and to serum estradiol-17β. Rapid changes in substrate affinity rather than changes in substrate concentration or de novo synthesis of the enzyme may thus be important for regulation of ovarian aromatase. The [11C]vorozole in vivo technique yields additional information compared with traditional in vitro techniques.

One-step photoinitiated free radical carbonylation was employed for the rapid (5–7 min) labelling of aliphatic carboxylic acids, esters, and amides with a short-lived positron emitter 11C (t½ = 20.3 min) at the carbonyl position. The labelled compounds were synthesized from alkyl iodides (0.05–0.1 mmol), [11C]carbon monoxide, and appropriate nucleophiles. Decay-corrected radiochemical yields were up to 74%; conversion of [11C]carbon monoxide reached 85–90%; specific radioactivity was 158–192 GBq/mmol. The labelled compounds were identified and characterized using HPLC, LC-MS, and 1H and 13C NMR. The effects of solvents, additives, photoirradiation, temperature, and reaction time were studied and discussed. [carbonyl-11C]Amides were synthesized using amines in 1–2 equiv. to iodides, exploiting solvent effects to control reactivity. [carboxyl-11C]Acids were synthesized using water as a nucleophile, in binary and ternary aqueous solvent mixtures; the addition of TBAOH or KOH was necessary to obtain high radiochemical yields. [carbonyl-11C]Esters were synthesized using primary and secondary alcohols, tert-butanol, and phenol. Bases were KOH, BuLi, LiHDMS. The effects of photosensitizers were studied and exploited to accelerate the labelling of carboxylic acids and esters resulting in 75–85% decay-corrected radiochemical yields under mild conditions without the use of bases. A mild procedure for the 11C-carboxylation of alkyl iodides using DMSO as an oxygen nucleophile was developed. This method is expected to be suitable in the macroscale synthesis of carboxylic acids using isotopically unmodified carbon monoxide. Radical carbonylation was applied to improve the synthesis of an extensively used PET tracer, [carbonyl-11C]WAY-100635. The tracer was synthesized in one step, whereas a common approach via Grignard reagents requires three steps. In addition, several (13C)compounds were synthesised using the described methods. Free radical carbonylation may be used for the 11C-carbonylation of alkyl iodides, whereas transition-metal carbonylation – of aryl halides and triflates. Thus, the two carbonylation methods are complementary with respect to the scope of synthetic targets.

The use of positron emission tomography (PET) for imaging in oncology has grown rapidly in recent years. 2-[18F]-fluorodeoxyglucose (FDG) is the most common tracer of PET, although drawbacks exist. Radiolabeled 1-[11C]-acetate (C-AC) is a simple probe for evaluation of perfusion, anabolism (lipogenesis) and catabolism (oxidative metabolism) in all living tissues. This study explored the potential of AC PET in head and neck cancer, benign and malignant lymph nodes in prostate cancer and normal distribution.  In head and neck cancer, C-AC PET detected more primaries and lymph node metastases than FDG PET. The mean primary tumor volumes delineated by C-AC was 51% larger than that of FDG before radiotherapy (RT). Both FDG and C-AC PET tumor volumes must be carefully validated before used in clinical routine. Baseline tumor clearance rate (kmono) was higher in complete responders (CR) than that in partial responders (PR). kmono tended to correlate inversely with FDG SUV at baseline. Radiosensitive tumors might rely predominantly on oxidative metabolism for their biogenetic needs. kmono increased in PR during RT. The potential reversibility of impaired kmono in radioresistant tumors imply that treatment targeting the intermediary metabolism might improve the outcome. Tumor relative perfusion index (rF) and kmono were coupled in CR throughout the RT, but not in PR. Dynamic C-AC PET provides a new non-invasive method to simultaneously evaluate the tumor oxidative metabolism and perfusion which link the RT response in patients by a single tracer injection. In prostate cancer, elevated C-AC accumulation is common in benign inguinal lymph nodes, probably due to increased lipogenesis rather than lymphatic drainage. CT Hounsfield unit of benign nodes was lower than that of metastases, suggesting that density measurement using CT might improve the specificity of nodal staging of prostate cancer. A novel tracer 2-[18F]-fluoroacetate (F-AC) was synthesized and used for dynamic PET-CT imaging in animals. Compared with C-AC PET-CT, F-AC showed prolonged blood retention, no detectable trapping in myocardium and salivary glands, rapid excretion from liver to bile and urine and de-fluorination resulting in intensive skeletal activity. F-AC does not mimic the normal physiologic path of C-AC and appears to be of little use for assessment of perfusion, intermediary metabolism or lipogenesis.

Introdução: A tomografia por emissão de pósitrons (PET) permite a avaliação in vivo de alvos moleculares em doenças neurodegenerativas, como a doença de Alzheimer (DA). A deposição de placa Beta-amiloide pode ser avaliada por PET 11C-PIB, enquanto o PET 18F-FDG é utilizado para avaliar o metabolismo da glicose cerebral, que pode ser um indicador de lesão neuronal e disfunção sináptica. Além disso, a captação cerebral precoce de radiofármacos de PETamiloide pode determinar o fluxo sanguíneo cerebral regional. Mais estudos correlacionando a fase inicial de perfusão do 11C-PIB (11C-pPIB) e 18F-FDG ainda são necessários, considerando que o fluxo sanguíneo e o metabolismo da glicose cerebral são geralmente acoplados em repouso e durante as ativações neuronais. Objetivo: Avaliar se existe concordância diagnóstica e/ou topográfica entre a imagem na fase de perfusão do 11C-PIB (11C-pPIB), obtida entre 0 e 10 minutos, e a imagem metabólica de PET 18F-FDG através da quantificação por SPM (Statistical Parametric Mapping) e por análise visual, em sujeitos com DA e CCLa comparados aos controles idosos saudáveis. Métodos: CAPEPesq: Nº1.454.598. Noventa e três sujeitos foram alocados em três grupos de acordo com o diagnóstico clínico: doença de Alzheimer (DA - n = 27); Comprometimento Cognitivo Leve amnéstico (CCLa - n = 39); Controle idosos saudáveis (n = 27), estes foram submetidos a exames de imagens de RM ponderada em T1 e de PET/CT. A PET/CT 18F-FDG foi realizada 30 minutos após a injeção do radiofármaco e a PET/CT 11C-pPIB foi adquirida imediatamente após a injeção do radiofármaco, e os primeiros 10 minutos da aquisição foram considerados na análise. Imagens de PET foram corrigidas para efeito de volume parcial e as imagens foram espacialmente normalizadas utilizando um modelo anatômico personalizado da própria amostra (template), para análise por Mapa Estatístico Paramétrico (SPM8). A análise visual e individual foi realizada por dois médicos nucleares com experiência na área, cegos em relação à identificação das imagens, seus respectivos radiofármacos e diagnóstico clínico. Eles foram solicitados a fornecer um diagnóstico e indicar uma classificação com base na inspeção visual das imagens de 18F-FDG e 11CpPIB, e também na avaliação individual dos mapas-t de SPM (análise baseada em voxel comparando um único sujeito do grupo DA com um grupo de controle cognitivamente normal). Resultados e Discussão: Na análise por SPM, o 11CpPIB mostrou menor captação difusa cortical do que 18F-FDG. Na análise entre grupos, há uma diferença na captação de 11C-pPIB e 18F-FDG, o que é esperado, uma vez que a biodistribuição é uma propriedade particular de cada biomarcador de PET. Na comparação do grupo DA em relação ao grupo controle, os indivíduos com DA apresentaram diminuição da captação de 11C-pPIB nas regiões temporo-límbicas: amígdala e hipocampo (E = esquerdo) P = 0,006, amígdala e hipocampo (D = direito) P = 0,023; giro parahipocampal (E) P = 0,008 (D) P = 0,015; temporal superior (E) P = 0,012 (D) P = 0,015. No 18F-FDG, houve diminuição da captação no grupo DA comparado ao grupo controle nas seguintes regiões: córtex do cíngulo posterior (E) P = 0,028; pré-cuneus (E) P= 0,029; giro temporal médio (E) P = 0,039; giro temporal inferior (E) P = 0,044. Na comparação do grupo CCLa em relação ao grupo controle, os indivíduos com CCLa apresentaram diminuição da captação de 11C-pPIB na região do giro parahipocampal (E) P = 0,012. Na identificação visual, 100% das imagens PET 18F-FDG e 99% das imagens PET 11C-pPIB foram corretamente identificadas. Na análise visual e individual, foram observadas reduções na captação de 11CpPIB envolvendo a região temporal medial nos indivíduos com DA que não foi detectada pelo 18F-FDG. Isso poderia significar algum tipo de dissociação entre a perfusão e o metabolismo. Conclusão: Nossos achados sugerem que não há concordância diagnóstica e topográfica perfeita entre a imagem do metabolismo de glicose por PET com 18F-FDG e o padrão de perfusão cerebral usando o marcador PET 11C-PIB em certas estruturas cerebrais em idosos saudáveis, CCLa e pacientes com DA, na quantificação por SPM e na análise visual. Como um biomarcador duplo, a PET 11C-pPIB pode fornecer informações complementares sobre alterações fisiológicas no envelhecimento, e ajudar a elucidar e entender melhor a patologia das doenças relacionadas a memória / Introduction: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer´s Disease (AD). Beta-amyloid plaque deposition can be assessed by 11C-PIB PET while 18FFDG PET is used to assess cerebral glucose metabolism, which can be an indicator for neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of PET-amyloid radiopharmaceuticals can determine regional cerebral blood flow. More studies correlating early-phase 11C-PIB (11C-pPIB) and 18F-FDG are still needed considering that blood flow and cerebral glucose metabolism are usually coupled at rest and during neuronal activations. The aim of this study is to evaluate topographic similarities and differences between cerebral perfusion images obtained with early 11C-PIB PET images and the metabolic images obtained with 18F-FDG PET. Methods: CAPEPesq: Nº1.454.598. Ninety-three subjects were allocated into three groups according to clinical diagnosis: Alzheimer\'s disease (AD, n=27); Mild Cognitive Impairment amnestic (aMCI, n=39); Elderly healthy control (n=27), they underwent T1-weighted MRI and PET/CT imaging. 18F-FDG PET/CT acquisition was performed 30 minutes after tracer injection and 11C-pPIB PET/CT was acquired immediately after the tracer injection and the first 10 minutes of the acquisition was considered in the analysis. PET images were corrected for partial volume effect and the images were spatially normalized using a custom anatomical template of the sample itself, for analysis by Statistical Parametric Mapping (SPM8). Visual and individual analysis were performed by two experient nuclear medicine physicians, blind in relation to the identification of the images, their respective radiopharmaceuticals and clinical diagnosis. They were asked to provide a diagnosis and to indicate their level of confidence on the basis of visual inspection of 18F-FDG and 11C-pPIB images, and also individual assessment of SPM t-maps (voxel-based analysis comparing a single subject of AD group to a cognitively normal control group). Results and Discussion: In the analysis by SPM, the 11C-pPIB showed lower cortical diffuse uptake than 18F-FDG. In the analysis between groups, there is a difference in 11CpPIB and 18F-FDG uptake, what is expected since biodistribution is a particular propriety of each PET tracer. The control group versus the AD group, individuals with AD presented a decreased 11C-pPIB uptake in the temporo-limbic regions: amygdala and hippocampal (L = left) P = 0.006; amygdala and hippocampal (R = right) P = 0.023; parahippocampal gyrus (L) P = 0.008 (R) P = 0.015; and superior temporal (L) P = 0.012 (R) P = 0.015. In the 18F-FDG, there was a decreased uptake in the AD group compared to the control group in the following regions: posterior cingulate cortex (L) P = 0.028; precuneus (L) P= 0.029; medial temporal gyrus (L) P = 0.039; and inferior temporal gyrus (L) P = 0.044. In the comparison of aMCI group versus the control group, individuals with aMCI presented a decreased 11C-pPIB uptake in the region: parahippocampal gyrus (L) P = 0.012. In the visual identification, 100% of 18F-FDG PET images and 99% of 11C-pPIB PET images were correctly recognized. In the visual and individual analysis, it was observed reductions in 11C-pPIB uptake involving medial temporal region in the AD subjects that was not detected by 18F-FDG.This could mean some kind of decoupling between perfusion and metabolism. Conclusion: Our findings suggest that there is no perfect diagnostic and topographical concordance between the imaging of 18F-FDG PET glucose and the cerebral perfusion pattern using the 11C-PIB PET marker in certain brain structures in healthy elderly, aMCI and patients suggestive of AD, quantification by SPM and visual analysis. As a double biomarker, 11C-PIB can provide complementary information on pathological aging of the brain, and it could help elucidate and better understand the pathology of memory-related diseases