Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Episodic Memory, Hippocampal Volume, and Function for Classification of Mild Cognitive Impairment Patients Regarding Amyloid Pathology.

BACKGROUND: Previous studies of hippocampal function and volume related to episodic memory deficits in patients with amnestic mild cognitive impairment (aMCI) have produced mixed results including increased or decreased activity and volume. However, most of them have not included biomarkers, such as amyloid-ß (Aß) deposition which is the hallmark for early identification of the Alzheimer's disease continuum. OBJECTIVE: We investigated the role of Aß deposition, functional hippocampal activity and structural volume in aMCI patients and healthy elderly controls (HC) using a new functional MRI (fMRI) ecological episodic memory task. METHODS: Forty-six older adults were included, among them Aß PET PIB positive (PIB+) aMCI (N = 17), Aß PET PIB negative (PIB-) aMCI (N = 15), and HC (N = 14). Hippocampal volume and function were analyzed using Freesurfer v6.0 and FSL for news headlines episodic memory fMRI task, and logistic regression for group classification in conjunction with episodic memory task and traditional neuropsychological tests. RESULTS: The aMCI PIB+ and PIB-patients showed significantly worse performance in relation to HC in most traditional neuropsychological tests and within group difference only on story recall and the ecological episodic memory fMRI task delayed recall. The classification model reached a significant accuracy (78%) and the classification pattern characterizing the PIB+ included decreased left hippocampal function and volume, increased right hippocampal function and volume, and worse episodic memory performance differing from PIB-which showed increased left hippocampus volume. CONCLUSION: The main findings showed differential neural correlates, hippocampal volume and function during episodic memory in aMCI patients with the presence of Aß deposition.

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study.

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.

18F-FDG PET/CT AS AN ASSESSMENT TOOL OF HEPATOCELLULAR CARCINOMA SECONDARY TO NON-ALCOHOLIC FATTY LIVER DISEASE DEVELOPMENT IN EXPERIMENTAL MODEL.

BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.

PET/CT com 18F-FDG como ferramenta de avaliação do desenvolvimento de carcinoma hepatocelular secundário a doença hepática gordurosa não alcoólica em modelo experimental / 18f-fdg pet/ct as an assessment tool of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease development in experimental model

ABSTRACT BACKGROUND: Hepatocellular carcinoma (HCC) can be the last step of non-alcoholic fatty liver disease (NAFLD) evolution. Experimental models are crucial to elucidate the pathogenesis of HCC secondary to NAFLD. The 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating HCC development and progression. OBJECTIVE: To standardize the imaging method of PET/CT with 18F-FDG as an evaluation tool of the experimental model of HCC secondary to NAFLD. METHODS: Ten male Sprague-Dawley rats were fed with choline-deficient high-fat diet and diethylnitrosamine (DEN) in the drinking water for 16 weeks and then received 1 mL of saline solution (0.9%) daily by gavage for three weeks. At the 16th and 19th weeks, abdominal ultrasonography (USG) was performed. 18F-FDG PET/CT images were obtained before the beginning of experiment (week 0) and at the end (week 19). Histological and immunohistochemically analysis were also performed. RESULTS: The USG results showed a homogeneous group at the 16th week with an average of 4.6±2.74 nodules per animal. At the 19th week, PET/CT findings demonstrated an average of 8.5±3.7 nodules per animal. The mean values of SUVmed and SUVmax were 2.186±0.1698 and 3.8±1.74, respectively. The average number of nodules per animal in the histological analysis was 5.5±1.5. From all nodules, 4.6% were classified as well-differentiated HCC and 81.8% were classified as poorly-differentiated HCC. CONCLUSION: 18F-FDG PET/CT was able to evaluate the development of HCC in an experimental model of NAFLD non-invasively. From the standardization of PET/CT in this model, it is possible to use this tool in future studies to monitor, in vivo and non-invasively, the progression of HCC.

RESUMO BACKGROUND: O carcinoma hepatocelular (CHC) pode ser a última fase da doença hepática gordurosa não alcoólica (DHGNA). Modelos experimentais são cruciais para elucidação da patogênese do CHC secundário a DHGNA. A tomografia por emissão de pósitrons/tomografia computadorizada (PET/TC) com 2-desoxi-2-(18F)fluoro-D-glicose (18F-FDG) desempenha um importante papel na avaliação do desenvolvimento e progressão do CHC. OBJETIVO: Padronizar a metodologia de imagem por PET/TC com 18F-FDG como uma ferramenta de avaliação do modelo experimental de CHC secundário a DHGNA. MÉTODOS: Dez ratos Sprague-Dawley machos foram alimentados com dieta hiperlipídica deficiente em colina associada a dietilnitrosamina (DEN) na água de beber por 16 semanas e depois receberam 1 mL de solução salina (0,9%) por gavagem diariamente por três semanas. Nas 16ª e 19ª semanas, foi realizada a ultrassonografia abdominal. As imagens do PET/TC com 18F-FDG foram obtidas antes do início do experimento (semana 0) e no final (semana 19). Análises histológica e imunohistoquímica também foram realizadas. RESULTADOS: Os resultados da ultrassonografia demonstraram um grupo homogêneo na 16ª semana com uma média de 4,6±2,74 nódulos por animal. Na 19ª semana, os achados do PET/CT demonstraram uma média de 8,5±3,7 nódulos por animal. Os valores médios de SUVmed e SUVmáx foram 2,186±0,1698 e 3,8±1,74, respectivamente. A média do número de nódulos na análise histológica foi de 5,5±1,5. De todos os nódulos, 4,6% foram classificados como bem diferenciados e 81,8% foram classificados como CHC pouco diferenciado. CONCLUSÃO: O PET/TC com 18F-FDG foi capaz de avaliar o desenvolvimento do CHC secundário a DHGNA de forma não invasiva. A partir da padronização do PET/CT neste modelo, faz-se possível a utilização desta ferramenta em futuros estudos para monitorar, in vivo e de forma não invasiva, a progressão do CHC.

Evaluation of GX1 and RGD-GX1 peptides as new radiotracers for angiogenesis evaluation in experimental glioma models.

Gliomas are the most common type among all central nervous system tumors. The aggressiveness of gliomas is correlated with the level of angiogenesis and is often associated with prognosis. The aim of this study is to evaluate the novel GX1 peptide and the heterodimer RGD-GX1 radiolabeled with technetium-99m, for angiogenesis detection in glioma models. Radiolabeling and radiochemical controls were assessed for both radioconjugates. In vitro binding studies in glioma tumor cells were performed, as well as biodistribution in SCID mice bearing tumor cells, in order to evaluate the biological behavior and tumor uptake of the radiocomplexes. Blocking and imaging studies were also conducted. MicroSPECT/CT images were acquired in animals with experimentally implanted intracranial tumor. Open field activity was performed to evaluate behavior, as well as perfusion and histology analysis. The radiochemical purity of both radiotracers was greater than 96 %. In vitro binding studies revealed rather similar binding profi le for each molecule. The highest binding was for RGD-GX1 peptide at 120 min in U87MG cells (1.14 ± 0.35 %). Tumor uptake was also favorable for RGD-GX1 peptide in U87MG cells, reaching 2.96 ± 0.70 % at 1 h p.i. with 47 % of blocking. Imaging studies also indicated better visualization for RGD-GX1 peptide in U87MG cells. Behavior evaluation pointed brain damage and histology studies confirmed actual tumor in the uptake site. The results with the angiogenesis seeking molecule (99m)Tc-HYNIC-E-[c(RGDfk)-c(GX1)] were successful, and better than with (99m)Tc-HYNIC-PEG4-c(GX1). Future studies targeting angiogenesis in other glioma and nonglioma tumor models are recommended.

PET imaging in multiple sclerosis.

Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus can be applied to detect and monitor different aspects of diseases. The number of applications of PET imaging in multiple sclerosis is still limited. Clinical studies using PET are basically focused on monitoring changes in glucose metabolism and the presence of activated microglia/macrophages in sclerotic lesions. In preclinical studies, PET imaging of targets for other processes, like demyelination and remyelination, has been investigated and may soon be translated to clinical applications. Moreover, more PET tracers that could be relevant for MS are available now, but have not been studied in this context yet. In this review, we summarize the PET imaging studies performed in multiple sclerosis up to now. In addition, we will identify potential applications of PET imaging of processes or targets that are of interest to MS research, but have yet remained largely unexplored.

Avaliação dos custos para realização de controles de qualidade de radiofármacos marcados com [99mTc]tecnécio em serviços de medicina nuclear no Brasil / Evaluation of costs for quality control of [99mTc]technetium radiopharmaceuticals in Brazilian nuclear medicine centers

OBJETIVO: Estabelecer os custos dos controles de qualidade para os radiofármacos marcados com [99mTc]tecnécio nos serviços de medicina nuclear do Brasil, em atenção às resoluções RDC nº 38/2008 e RDC nº 63/2009 editadas pela Agência Nacional de Vigilância Sanitária. MATERIAIS E MÉTODOS: Foram apurados preços de materiais de consumo, equipamentos e de mão-de-obra para a realização dos controles de qualidade. Os valores foram convertidos para unidades de volume, tempo e outras unidades cabíveis para a determinação do preço unitário. RESULTADOS: O investimento para aquisição de materiais de consumo e equipamentos foi estimado ser de R$ 35.500,00. O custo final para o controle de cada kit variou entre R$ 6,44 e R$ 7,80, dependendo do produto a ser analisado e do profissional selecionado para execução do procedimento. Esses valores podem representar de 0,5 por cento a 10 por cento do valor recebido pelas instituições pela realização dos exames. Na prática, o custo efetivo pode ser menor, uma vez que o produto de um kit pode ser utilizado em diversos pacientes. CONCLUSÃO: Em face do ganho de qualidade e segurança dos pacientes, concluímos que os custos da implantação do programa de controle de qualidade podem ser absorvidos no planejamento financeiro dos serviços de medicina nuclear.

OBJECTIVE: To establish the costs for quality control of [99mTc]technetium radiopharmaceuticals in Brazilian nuclear medicine centers, in compliance with Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency) resolutions RDC No. 38/2008 and No. 63/2009. MATERIALS AND METHODS: Prices for consumables, equipment and labor involved in quality control procedures were calculated and the values were converted into units of volume, time or other appropriate units for use in mathematical formulas for determining unit prices. RESULTS: Estimated investment for acquisition of consumables and equipment was R$ 35,500.00. The final unit cost for quality control of a [99mTc]technetium radiopharmaceutical kit ranged from R$ 6.44 to R$ 7.80 per kit, depending on the product under analysis, on the methodology applied and on the qualification of the professional involved in the process. Such values may correspond to 0.5 percent to 10 percent of the amount received by the institution per diagnostic procedure. In practice the effective cost might be lower, considering that a single labeled kit can be fractionated into several doses. CONCLUSION: Considering the gains in quality and patients' safety, the authors conclude that costs for implementing a quality control program for radiopharmaceuticals can be absorbed in the financial planning of nuclear medicine centers.