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1.
Clin Nucl Med ; 44(12): 949-955, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31689275

RESUMO

INTRODUCTION: Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune dysregulatory condition, usually presenting in childhood with massive lymphadenopathy, splenomegaly, and an increased incidence of lymphoma. Methods to differentiate between benign ALPS adenopathy and lymphoma are needed. To this end, we evaluated the usefulness of FDG PET. METHODS: We prospectively evaluated 76 ALPS/ALPS-like patients including FS-7-associated surface antigen (FAS) germline mutation with (n = 4) and without lymphoma (n = 50), FAS-somatic (n = 6), ALPS-unknown (n = 6), and others (n = 10) who underwent FDG PET. Uptakes in 14 nodal sites, liver, and spleen were determined. RESULTS: In 76 ALPS patients, FDG PET showed uptake in multiple nodal sites in all but 1 patient. The highest SUVmax values in FAS mutation without lymphoma, FAS mutation with lymphoma, FAS somatic, ALPS-unknown, and other genetic mutations were a median (range) 9.2 (4.3-25), 16.2 (10.7-37.2), 7.6 (4.6-18.1), 11.5 (4.8-17.2), and 5.5 (0-15.3), respectively. Differences between uptake in the FAS group with and without lymphoma were statistically significant, but overlapped, making discrimination between individuals with/without lymphoma impossible. The spleen:liver uptake ratio was greater than 1 in 82% of patients. CONCLUSIONS: While statistically significant differences were observed in FAS mutation ALPS with and without lymphoma, the significant overlap in FDG uptake and visual appearance in many patients prevents discrimination between patients with and without lymphoma. Similar patterns of FDG biodistribution were noted between the various ALPS subgroups.


Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Adolescente , Adulto , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/metabolismo , Criança , Pré-Escolar , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Linfoma/complicações , Masculino , Mutação , Esplenomegalia/complicações , Distribuição Tecidual , Adulto Jovem , Receptor fas/genética
2.
Br J Radiol ; 92(1104): 20190380, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31600089

RESUMO

OBJECTIVE: To evaluate the therapeutic response, progression free survival (PFS), overall survival (OS) and clinical toxicity of 177Lu-PSMA-617 PSMA targeted radioligand therapy (PRLT) in the setting of heavily pre-treated metastatic castrate-resistant prostate cancer (mCPRC) patients and also examine the association of prognostic variables with therapeutic outcome in such patient cohort. METHODS: We examined the medical records of mCRPC patients who had undergone 177Lu-PSMA-617 PRLT from March 2017 to February 2019 in our institute. Patients receiving equal to or more than two cycles were included and analyzed in this retroprospective study.The 68Ga-PSMA-11 PET-CT and 18-fludeoxyglucose positron emission tomography (18FDG PET)-CT scan findings, serum prostate-specific antigen (PSA) change, health-related quality of life (HRQoL) scales (Eastern Cooperative Oncology Group/Karnofsky score) and Gleason score were assessed for their implications on the outcome of therapy. The treatment response was evaluated under three categories: (a) symptomatic (b) biochemical and (c) imaging response.The PFS and OS following first PRLT were determined and the association of various variables with PSA doubling time (DT) and FDG uptake in the lesions were analyzed. Toxicity assessment was undertaken objectively by National Cancer Institute-Common Terminology Criteria for Adverse Events scale v. 5.0 for haematological and nephrotoxicity, and salivary gland toxicity assessed by xerostomia inventory score. RESULTS: A total of 40 mCRPC patients (age range: 46-84 years; median 63 years), who had undergone 177Lu-PSMA-617 PRLT, of at least two cycles was identified and selected for the analysis. FDG uptake was noted in 87.5% of patients (n = 35). Out of 40 cases, 21 were responders (CR, PR and SD) and 19 were non-responders (PD) on symptomatic and biochemical scales while on molecular imaging response, 16 (43%) were responders and remaining 21 (57%) were non-responders. Lesion-wise, 68Ga-PSMA-11 avid metastatic nodal disease responded well with 177Lu PSMA-617 PRLT, as compared to hepatic and skeletal lesions. The median OS and PFS was 12 and 7 months respectively following first PRLT. Patients with negative serum PSA-DT demonstrated superior 1 year PFS as compared to those with positive serum PSA-DT (52.5 vs 47.5%) (p = 0.029). Patients receiving greater than two cycles PRLT demonstrated a higher negative PSA-DT as compared to those receiving two cycles (p-value = 0.03). Grade 1 xerostomia was observed in two patients (5%) (mean xerostomia score of 23), haematotoxicity in seven patients [Grade I (n = 2, 5%) and Grade II (n = 5, 14%)]. CONCLUSION: 177Lu-PSMA-617 PRLT was well-tolerated and able to produce disease control with good symptomatic and biochemical responses in the context of heavily pre-treated mCRPC with progressive disease, with low toxicity profile. Evident association of high FDG uptake was observed with aggressive disease biology coupled with increasing Gleason score and poorer 12 months PFS. Negative PSA-DT following therapy demonstrated longer PFS. The results demonstrate important future role of 177Lu-PSMA-617 PRLT in the treatment of mCRPC. ADVANCES IN KNOWLEDGE: The present work explored in a large teriary cancer care setting, the efficacy of 177Lu-PSMA-617 PRLT, in an aggressive and unselected subset of mCRPC. The response and outcome was correlated with a number of prognostic variables, including molecular imaging findings (FDG uptake in the metastatic lesions), PSA DT and Gleason score.


Assuntos
Dipeptídeos/uso terapêutico , Fluordesoxiglucose F18/farmacocinética , Glutamato Carboxipeptidase II/antagonistas & inibidores , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície , Dipeptídeos/efeitos adversos , Radioisótopos de Gálio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Lutécio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Gradação de Tumores , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Radioisótopos/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(31): e16690, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374056

RESUMO

This study investigated the clinicopathologic factors associated with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.Two hundred twenty-nine retrospectively enrolled patients underwent preoperative F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting F-FDG uptake (all P < .05). According to multivariate analysis, location (lower 3rd, P = .035), gross type (0-I, 0-IIa, P < .001), size (≥2.5 cm, P = .026), and depth of invasion (submucosa, P = .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Neoplasias Gástricas/diagnóstico por imagem , Adenocarcinoma/patologia , Adulto , Idoso , Detecção Precoce de Câncer/métodos , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Neoplasias Gástricas/patologia
4.
Medicine (Baltimore) ; 98(27): e16306, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277170

RESUMO

This study investigated the effect of sex hormones on F-fluorodeoxyglucose (FDG) uptake in normal breast tissue.The retrospective study included 249 premenopausal women (median age, 45 years) who were diagnosed with unilateral breast cancer and underwent FDG positron emission tomography/computed tomography and hormone tests. The volume of interest was within the contralateral normal breast and the standardized uptake values (SUVs) were measured. The correlations of sex hormones (including estrogen, progesterone, testosterone, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with the SUVs of the normal breast were analyzed.There was a weak negative correlation between age and breast FDG uptake (P = .012, Spearman coefficient = -.16 for the maximum standardized uptake values [SUVmax]), especially in the luteal phase group (P = .005, Spearman coefficient = -.27 for SUVmax). The SUVs of normal breast tissue were increased when progesterone levels were higher (P = .043, Spearman coefficient = .13 for SUVmax). In the irregular menstrual cycle group, FDG uptake in the breast decreased as FSH (P = .027, Spearman coefficient = -.42 for SUVmax) and LH (P = .048, Spearman coefficient = -.44 for SUVmax) increased.Glucose metabolism of normal breast tissue decreases with age, and progesterone weakly affects breast FDG uptake. Gonadotropins may affect breast FDG uptake in premenopausal women with irregular menstrual cycles.


Assuntos
Mama/metabolismo , Estradiol/sangue , Fluordesoxiglucose F18/farmacocinética , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Progesterona/sangue , Testosterona/sangue , Adulto , Mama/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Valores de Referência , Estudos Retrospectivos
5.
Eur Radiol ; 29(12): 6717-6727, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31278574

RESUMO

OBJECTIVES: We recently described metabolic nodal stage (mN) and response (mNR) of cancer of the esophagus and gastro-esophageal junction (GEJ) to neoadjuvant chemotherapy (NAC) using 18F-FDG PET-CT as new markers of disease progression, recurrence, and death. We aimed to validate our findings. METHODS: Our validation cohort comprised all patients consecutive to our discovery cohort, staged before and after NAC using PET-CT from 2014 to 2017. Multivariate binary logistic and Cox regression were performed. RESULTS: Fifty-one of the 200 patients had FDG-avid nodes after NAC (25.5%; i.e., lack of complete mNR), and were more likely to progress during NAC to incurable disease on PET-CT or at surgery: odds ratio 3.84 (1.46-10.1; p = 0.006). In 176 patients undergoing successful resection, patients without complete mNR had a worse prognosis: disease-free survival hazard ratio 2.46 (1.34-4.50); p = 0.004. These associations were independent of primary tumor metabolic, pathological response, and stage. In a hybrid pathological/metabolic nodal stage, avid nodal metastases conferred a worse prognosis than non-avid metastases. Lack of complete mNR predicted recurrence or death at 1 and 2 years: positive predictive values 44.4% (31.7-57.8) and 74.1% (56.6-86.3) respectively. CONCLUSIONS: This study provides temporal validation for mNR as a new and independent predictive and prognostic marker of esophageal and GEJ cancer treated with NAC and surgery, although external validation is required to assess generalizability. mNR may provide surrogate information regarding the phenotype of metastatic cancer clones beyond the mere presence of nodal metastases, and might be used to better inform patients, risk stratify, and personalize management, including adjuvant therapy. KEY POINTS: • We previously described metabolic nodal response (mNR) of esophageal cancer to neoadjuvant chemotherapy using 18 F-FDG PET-CT as a predictor of unresectable disease, early recurrence, and death. • We report the first validation of these findings. In an immediately consecutive cohort, we found consistent proportions of patients with and without mNR, and associations with abandoned resection, early recurrence, and death. • This supports mNR as a new and actionable biomarker in esophageal cancer. Although external validation is required, mNR may provide surrogate information about the chemosensitivity of metastatic subclones, and the means to predict treatment success, guide personalized therapy, and follow-up.


Assuntos
Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/tratamento farmacológico , Fluordesoxiglucose F18/farmacocinética , Linfonodos/metabolismo , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/metabolismo , Junção Esofagogástrica/diagnóstico por imagem , Junção Esofagogástrica/metabolismo , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Resultado do Tratamento
6.
Int J Radiat Oncol Biol Phys ; 105(2): 356-366, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31254659

RESUMO

PURPOSE: To assess whether radiographic and metabolic changes on midchemoradiation therapy (CRT) fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for cervical cancer predict outcome. METHODS AND MATERIALS: Women with International Federation of Gynecology and Obstetrics stage IB1-IVB cervical cancer treated with concurrent cisplatin-based CRT and brachytherapy were enrolled on a single-institution prospective clinical trial; FDG-PET/CT was obtained before CRT and at 30 to 36 Gy. Max and mean standard uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) for the primary tumor and clinically involved lymph nodes from the pre-CRT and intra-CRT FDG-PET/CT were recorded. Clinical endpoints analyzed include overall survival (OS), disease-free survival (DFS), and rates of cervical recurrence (CR), nodal recurrence (NR), and distant metastasis (DM). FDG-PET/CT variables and other prognostic factors associated with clinical endpoints were identified via univariate Cox proportional hazards modeling and competing risk analysis. RESULTS: Thirty women were enrolled from 2012 to 2016. After a median follow-up of 24 months, 2-year rates of OS, DFS, DM, NR, and CR were 68% (95% confidence interval [CI], 51%-85%), 44% (95% CI, 26%-63%), 42% (95% CI, 23%-59%), 14% (95% CI, 4%-30%), and 10% (95% CI, 2%-24%), respectively. Intra-PET metrics and TLG across all PET scans were most consistently associated with OS, DFS, DM, and NR on univariate analysis. Intra-CRT TLG was associated with OS (hazard ratio [HR] 1.35; 95% CI, 1.15-1.55; P = .001), DFS (HR 1.19; 95% CI, 1.04-1.34; P = .018), and NR (HR 1.25; 95% CI, 1.10-1.40; P = .002). No absolute or relative changes between parameters of baseline and mid-CRT FDG-PET/CT were associated with disease outcomes on univariate analysis, with the exception of relative change in mean standard uptake values and CR (P = .004). CONCLUSIONS: In this group of patients with high-risk cervical cancer treated with CRT and brachytherapy, TLG and metabolic tumor volume on intra-CRT FDG-PET/CT was associated with OS. These metrics may provide an early signal for selective treatment intensification with either dose escalation or adjuvant chemotherapy.


Assuntos
Quimiorradioterapia/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Fluordesoxiglucose F18/farmacocinética , Glicólise , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radiossensibilizantes/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
7.
Crit Rev Oncol Hematol ; 141: 73-81, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252322

RESUMO

This study aimed to assess the false-positive proportion of follow-up 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in lymphoma patients who initially achieved an end-of-treatment complete remission, using biopsy as reference standard. Medline was searched for original studies, studies were methodologically evaluated and results were meta-analytically summarized. Proportion of false-positive results ranged between 9.5%-90.0%, with a weighted summary proportion (random effects) of 42.9% (95% confidence interval [CI]: 29.0%-58.0%). A separate subgroup analysis in symptomatic patients only again revealed a relatively high summary proportion of false-positive follow-up FDG-PET of 37.5% (random effects). In conclusion, the false-positive proportion of follow-up FDG-PET in lymphoma patients who initially achieved an end-of-treatment complete remission is high and remains high when a combination of clinical symptoms and follow-up FDG-PET is used. Therefore, biopsy remains compulsory and follow-up FDG-PET alone may be regarded as unreliable to define progression-free survival.


Assuntos
Fluordesoxiglucose F18 , Linfoma/diagnóstico , Monitorização Fisiológica , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Reações Falso-Positivas , Feminino , Fluordesoxiglucose F18/farmacocinética , Seguimentos , Humanos , Linfoma/epidemiologia , Linfoma/metabolismo , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/normas , Monitorização Fisiológica/estatística & dados numéricos , Tomografia por Emissão de Pósitrons/normas , Indução de Remissão , Adulto Jovem
8.
BMB Rep ; 52(7): 457-462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31186081

RESUMO

[18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers. [BMB Reports 2019; 52(7): 457-462].


Assuntos
ATPases Associadas a Diversas Atividades Celulares/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/antagonistas & inibidores , ATPases Associadas a Diversas Atividades Celulares/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cromonas/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta a Droga , Feminino , Transportador de Glucose Tipo 1/antagonistas & inibidores , Transportador de Glucose Tipo 1/metabolismo , Hexoquinase/antagonistas & inibidores , Hexoquinase/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Morfolinas/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo
9.
Eur Radiol ; 29(12): 6708-6716, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31250167

RESUMO

OBJECTIVE: To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). METHODS: Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. RESULTS: DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p < 0.001). SUVPROX/SUVMLT ratios in DM and their controls also differed significantly (p = 0.0012). The SUVPROX/SUVMLT ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%). CONCLUSION: A muscle-to-muscle SUVPROX/SUVMLT ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis. KEY POINTS: • [18F]-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM). • A ratio of SUV in proximal muscles (SUVPROX) to SUV in musculus longissimus thoracis (SUVMLT) could be used to determine active DM. • Active disease is suspected for SUV PROX /SUV MLT ratios greater than 1.73.


Assuntos
Dermatomiosite/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Músculo Esquelético/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatomiosite/metabolismo , Dermatomiosite/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
PLoS One ; 14(5): e0216954, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31086392

RESUMO

BACKGROUND: Blocking the PD-1 pathway induces immune-related adverse events (irAEs) which often involve the thyroid gland (thyroid irAEs). Clinical features of a thyroid irAE including its predictability and relationship to prognosis remain to be elucidated. METHODS: Two hundred consecutive patients treated with nivolumab at Kyoto University Hospital between September 1, 2014 and August 31, 2017 were included in a retrospective cohort study. We systematically determined and classified subclinical and overt thyroid irAEs based on data collected of serum free T4 and TSH levels. Baseline characteristics and detailed clinical data were analyzed, and analyses of overall survival (OS) excluded patients censored within 1 month from the first administration of nivolumab. RESULTS: Sixty-seven patients (33.5%) developed thyroid irAEs and these were divided into a subclinical thyroid irAE group (n = 40, 20.0%) and an overt thyroid irAE group (n = 27, 13.5%). Patients with thyroid uptake of FDG-PET before treatment showed high incidences of overt thyroid irAE (adjusted odds ratio 14.48; 95% confidence interval [CI] 3.12-67.19), while the same relationship was not seen with subclinical thyroid irAE. Regarding the total cohort, the thyroid irAE (+) group had a significantly longer median OS than the thyroid irAE (-) group (16.1 versus 13.6 months, hazard ratio [HR] 0.61; 95% CI 0.39-0.93). In 112 non-excluded patients with lung cancer, the thyroid irAE (+) group similarly had a longer median OS than the thyroid irAE (-) group (not reached versus 14.2 months, HR 0.51; 95% CI 0.27-0.92). However, this observation was not seen in 41 non-excluded patients with malignant melanoma (12.0 versus 18.3 months, HR 1.54; 95% CI 0.67-3.43). CONCLUSIONS: By thyroid uptake of FDG-PET, overt thyroid irAEs could be predicted before nivolumab therapy. Thyroid irAEs related to good prognosis in lung cancer but might be inconclusive in malignant melanoma.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Nivolumabe/efeitos adversos , Neoplasias Cutâneas/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Tireoidite/diagnóstico por imagem , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Melanoma/tratamento farmacológico , Melanoma/imunologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Tireoidite/induzido quimicamente , Tireoidite/mortalidade , Tireoidite/patologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
11.
Int J Mol Sci ; 20(10)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137758

RESUMO

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr's tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Radioisótopos de Cobre/farmacocinética , Mieloma Múltiplo/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Sindecana-1/imunologia , Zircônio/farmacocinética , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Neoplasias Ósseas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Radioisótopos de Cobre/efeitos adversos , Radioisótopos de Cobre/química , Feminino , Fluordesoxiglucose F18/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL , Mieloma Múltiplo/patologia , Radioisótopos/efeitos adversos , Radioisótopos/química , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/química , Sindecana-1/química , Distribuição Tecidual , Zircônio/efeitos adversos , Zircônio/química
12.
Br J Radiol ; 92(1099): 20180668, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30982333

RESUMO

OBJECTIVES: This pilot study investigated the association of four PET image features and cyclo-oxygenase-2 (COX-2) expression in patients with oesophageal adenocarcinoma. The prognostic significance of these biomarkers was also assessed. METHODS: 50 consecutive patients [median age = 68 (range 47 - 84), males = 45) with oesophageal adenocarcinoma had PET/CT staging between January 2011 and July 2015. The maximum and mean standardised uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) were calculated from the primary tumour. Their association with COX-2 status was assessed using Mann-Whitney U tests. Kaplan-Meier and Cox regression analysis tested their prognostic significance. A p-value < 0.05 was considered statistically significant. RESULTS: 32 tumours (64.0%) were COX-2 positive. There was a significant association between SUVmean and COX-2 status (p = 0.019). TLG (hazard ratio (HR) 1.001, 95 % confidence intervals (CI) 1.000 - 1.002, p = 0.018) was significantly associated with overall survival on multivariable analysis. CONCLUSIONS: This study investigated the association between PET image features and COX-2 expression in oesophageal adenocarcinoma. The preliminary results signal that a combination of TLG (calculated as product of MTV and SUVmean) and COX-2 status may be a strong and clinically important prognostic biomarker. Our research group are planning a prospective, multi-centre study to validate these findings. ADVANCES IN KNOWLEDGE: Mean standardised uptake value (SUVmean) on PET imaging is associated with COX-2 expression in oesophageal adenocarcinoma.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Ciclo-Oxigenase 2/metabolismo , Neoplasias Esofágicas/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Adenocarcinoma/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Neoplasias Esofágicas/metabolismo , Esôfago/diagnóstico por imagem , Esôfago/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos
13.
PLoS One ; 14(4): e0215276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31034496

RESUMO

PURPOSE: This study aimed to elucidate whether muscle activity (in terms of glucose uptake) between the legs can be considered symmetrical during walking. Furthermore, we aimed to determine whether the [18F]-fluorodeoxyglucose was distributed heterogeneously throughout each muscle, and if so, whether areas of high uptake would be clustered. METHODS: Ten healthy participants walked on a treadmill at self-selected comfortable walking speed for a total of 90 minutes, 60 minutes before and 30 minutes after intravenous injection of 50 MBq [18F]-fluorodeoxyglucose. Thereafter, a positron emission tomography/computed tomography scan of the lower limb was acquired. Three-dimensional muscle contours of 78 (= 39x2) muscles of the left and right lower limb were semi-automatically determined from magnetic resonance imaging scans. After non-rigid registration, those muscle contours were used to extract [18F]-fluorodeoxyglucose uptake from the positron emission tomography scans. RESULTS: Large asymmetries were observed in the lower leg muscles (e.g. median absolute asymmetry index of 42% in the gastrocnemius medialis) and in the gluteus minimus (30% asymmetry) and gluteus medius (15% asymmetry), whereas the uptake in the thighs was relatively symmetrical between the limbs (<6% asymmetry). These were not related to limb-dominance nor to inter-limb differences in muscle volume. The [18F]-fluorodeoxyglucose distribution was not distributed normally; most voxels had a relatively low standardized uptake value, and a minority of voxels had a relatively high standardized uptake value. The voxels with higher [18F]-fluorodeoxyglucose uptake were distributed heterogeneously; they were clustered in virtually all muscles. CONCLUSION: The findings in this study challenge the common assumption of symmetry in muscle activity between the limbs in healthy subjects. The clustering of voxels with high uptake suggests that even in this prolonged repetitive task, different spatial regions of muscles contribute differently to walking than others.


Assuntos
Glucose/metabolismo , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Caminhada/fisiologia , Adulto , Transporte Biológico Ativo , Feminino , Fluordesoxiglucose F18/farmacocinética , Voluntários Saudáveis , Humanos , Imagem Tridimensional , Extremidade Inferior/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Adulto Jovem
14.
Appl Radiat Isot ; 148: 152-159, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959352

RESUMO

One of the hallmarks of cancer is increased cell proliferation. Measurements of cell proliferation by estimation of DNA synthesis with several radiolabeled nucleosides have been tested to assess tumor growth. Deoxycytidine can be phosphorylated by deoxycytidine kinase (dCK) and is incorporated into DNA. This study evaluated a radiofluorinated deoxycytidine analog, 5-[18F]fluoro-2'-deoxycytidine ([18F]FdCyd), as a proliferation probe and compared it with 5-[18F]fluoro-2'-deoxyuridine ([18F]FdUrd), 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), and [18F]fluorodeoxyglucose ([18F]FDG) in a tumor-bearing mouse model. [18F]FdCyd was synthesized from two precursors by direct electrophilic substitution. The serum stability and partition coefficient of [18F]FdCyd were evaluated in vitro. Positron emission topography (PET) imaging of Lewis lung carcinoma (LLC)-bearing mice with [18F]FdCyd, [18F]FdUrd, [18F]FLT, and [18F]FDG were evaluated. [18F]FdCyd was stable in mouse serum and normal saline for up to 4 h. With all radiotracers except [18F]FLT, PET can clearly delineate the tumor lesion. [18F]FdCyd and [18F]FdUrd showed high accumulation in the liver and kidney. The SUV and tumor-to-muscle (T/M) ratios derived from PET imaging of the radiotracers were [18F]FDG > [18F]FdCyd > [18F]FdUrd > [18F]FLT. Selective retention in tumors with a favorable tumor/muscle ratio makes [18F]FdCyd a protential candidate for further investigation as a proliferation imaging agent.


Assuntos
Desoxicitidina/análogos & derivados , Floxuridina/administração & dosagem , Fluordesoxiglucose F18/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Animais , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Desoxicitidina/sangue , Desoxicitidina/farmacocinética , Floxuridina/farmacocinética , Fluordesoxiglucose F18/farmacocinética , Xenoenxertos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual
15.
Eur J Clin Invest ; 49(7): e13120, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31002171

RESUMO

BACKGROUND: Disturbances in adipose tissue glucose uptake may play a role in the pathogenesis of type 2 diabetes, yet its examination by 2-deoxy-2-[18 F]fluorodeoxyglucose ([18 F]FDG) PET/CT is challenged by relatively low uptake kinetics. We tested the hypothesis that performing [18 F]FDG PET/CT during a hypoglycaemic clamp would improve adipose tissue tracer uptake to allow specific comparison of adipose tissue glucose handling between people with or without type 2 diabetes. DESIGN: We enrolled participants with or without diabetes who were at least overweight, to undergo a hyperinsulinaemic hypoglycaemic clamp or a hyperinsulinaemic euglycaemic clamp (n = 5 per group). Tracer uptake was quantified using [18 F]FDG PET/CT. RESULTS: Hypoglycaemic clamping increased [18 F]FDG uptake in visceral adipose tissue of healthy participants (P = 0.002). During hypoglycaemia, glucose uptake in visceral adipose tissue of type 2 diabetic participants was lower as compared to healthy participants (P < 0.0005). No significant differences were observed in skeletal muscle, liver or pancreas. CONCLUSIONS: The present findings indicate that [18 F]FDG PET/CT during a hypoglycaemic clamp provides a promising new research tool to evaluate adipose tissue glucose metabolism. Using this method, we observed a specific impairment in visceral adipose tissue [18 F]FDG uptake in type 2 diabetes, suggesting a previously underestimated role for adipose tissue glucose handling in type 2 diabetes.


Assuntos
Tecido Adiposo/metabolismo , Hipoglicemia/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Fluordesoxiglucose F18/farmacocinética , Glucose/administração & dosagem , Glucose/farmacocinética , Humanos , Hipoglicemia/metabolismo , Hipoglicemiantes/administração & dosagem , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Edulcorantes/administração & dosagem , Edulcorantes/farmacocinética
16.
Nucl Med Commun ; 40(5): 552-554, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30973842

RESUMO

The numerator and denominator of the left-hand side of the Gjedde-Patlak-Rutland (GPR) equation for measurement of blood fluorine-18 fluorodeoxyglucose (F-FDG) clearance into tissue (Ki) are the standardized uptake values (SUVs) of tissue and blood, respectively. The extent to which normalized time (NT) in the GPR equation exceeds real time depends on half-time of clearance of F-FDG from blood. A literature review shows that NT is fairly constant, about 100 min at 60 min postinjection of F-FDG, in keeping with our own finding of no significant difference in maximum SUV in blood 60 min postinjection of F-FDG between 39 patients with F-FDG-avid malignancy on routine PET/CT (1.74±0.31) and 21 patients with normal PET/CT (1.79±0.32), and similar blood glucose levels (BGLs). Volume of distribution (V0) in the GPR equation is ∼0.4 ml/ml for brain and ∼0.9 ml/ml for lean liver. Using these values of V0 and an NT of 100 min, we used the GPR equation to calculate Ki from our own published values of SUVliver/SUVblood and SUVbrain/SUVblood at 60 min postinjection, obtaining 0.0045 ml/min/ml for liver and 0.036 ml/min/ml for brain at BGL of 5 mmol/l. These values for Ki at this BGL are close to literature values of Ki, which for liver and brain are ∼0.0033 and ∼0.035 ml/min/ml, respectively. We conclude, therefore, that following division with blood pool SUV, tissue SUV becomes a closer surrogate of Ki. This division also eliminates the controversy over which whole body metric to use in the calculation of SUV.


Assuntos
Encéfalo/metabolismo , Fluordesoxiglucose F18/sangue , Fluordesoxiglucose F18/farmacocinética , Fígado/metabolismo , Transporte Biológico , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Humanos , Fígado/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas , Padrões de Referência , Distribuição Tecidual
17.
Int J Cardiovasc Imaging ; 35(5): 955-964, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30706352

RESUMO

To develop and test a model predicting 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone [18F]FDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from - 0.01 ± 0.08 in ASC to - 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to - 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aorta Torácica/diagnóstico por imagem , Fluordesoxiglucose F18/farmacocinética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Veia Cava Inferior/diagnóstico por imagem , Adulto , Idoso , Aorta Abdominal/metabolismo , Aorta Torácica/metabolismo , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos/administração & dosagem , Reprodutibilidade dos Testes , Distribuição Tecidual , Veia Cava Inferior/metabolismo
18.
Mol Imaging ; 18: 1536012118821032, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799682

RESUMO

OBJECTIVE: To evaluate the preclinical value of 18F-fluoropropionic acid (18F-FPA) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for imaging HCCs. METHODS: The 18F-FPA and 18F-FDG uptake patterns in 3 HCC cell lines (Hep3B, HepG2, and SK-Hep1) were assessed in vitro and in vivo. The 18F-FPA uptake mechanism was investigated using inhibition experiments with orlistat and 5-tetradecyloxy-2-furoic acid. The 18F-FPA PET imaging was performed in different tumor animal models and compared with 18F-FDG. We also evaluated the expressions of glucose transporter-1 (GLUT1), fatty acid synthase (FASN), and matrix metalloproteinase-2 (MMP2) in these cell lines. RESULTS: In vitro experiments showed that the radiotracer uptake patterns were complementary in the HCC cell lines. Orlistat and 5-tetradecyloxy-2-furoic acid decreased the uptake of 18F-FPA. The tumor-to-liver ratio of 18F-FPA was superior to that of 18F-FDG in the SK-Hep1 and HepG2 tumors ( P < .05). However, in the Hep3B tumors, the tumor-to-liver normalized uptake of 18F-FDG was higher than 18F-FPA ( P < .01). FASN was highly expressed in cell lines with high 18F-FPA uptake, whereas GLUT1 was highly expressed in cell lines with high 18F-FDG uptake. The 18F-FPA uptake correlated with FASN ( r = 0.89, P = .014) and MMP2 ( r = 0.77, P = .002) expressions. CONCLUSIONS: PET imaging with 18F-FPA combined with 18F-FDG can be an alternative for detecting HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Ácido Graxo Sintase Tipo I/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Metaloproteinase 2 da Matriz/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Fluordesoxiglucose F18/administração & dosagem , Fluordesoxiglucose F18/farmacocinética , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Transplante de Neoplasias , Orlistate/administração & dosagem , Orlistate/farmacologia , Tomografia por Emissão de Pósitrons , Propionatos/administração & dosagem , Propionatos/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , Regulação para Cima
19.
Continuum (Minneap Minn) ; 25(1): 101-127, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30707189

RESUMO

PURPOSE OF REVIEW: This article reviews two of the primary progressive aphasias (PPAs), disorders characterized by the early and predominant impairment of language, and primary progressive apraxia of speech, a degenerative motor speech disorder that is closely related to PPA. An outline of the history and controversy surrounding how these disorders are classified is provided before the article focuses on each disorder's clinical and imaging features. RECENT FINDINGS: Over the past decade, the classification of degenerative speech and language disorders has been refined. Clinical, imaging, and pathologic evidence suggests that primary progressive apraxia of speech is a distinct degenerative disorder. Furthermore, multiple lines of evidence have highlighted issues with nonfluent/agrammatic variant PPA, which complicates the diagnosis, prognosis, and study of this disorder. Semantic variant PPA, while not without controversy, remains one of the most well-defined disorders, with good clinicopathologic correlation. SUMMARY: Accurate classification and diagnosis of these degenerative speech and language disorders is crucial in clinical practice and ongoing research efforts. For nonfluent/agrammatic variant PPA, the authors suggest emphasizing agrammatism as the core inclusion criterion and taking care not to include patients with isolated or predominant apraxia of speech. Isolated apraxia of speech can be the manifestation of a degenerative disease and, based on the different prognosis, should be recognized as distinct from PPA. Finally, it is important to recognize that some patients with semantic dementia, despite sharing the same pathologic associations, may not meet criteria for PPA.


Assuntos
Afasia Primária Progressiva/fisiopatologia , Apraxias/fisiopatologia , Fala/fisiologia , Idoso , Afasia Primária Progressiva/diagnóstico , Afasia Primária Progressiva/epidemiologia , Afasia Primária Progressiva/genética , Apraxias/diagnóstico , Apraxias/epidemiologia , Apraxias/genética , Encéfalo/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18/farmacocinética , Demência Frontotemporal/etiologia , Humanos , Imagem por Ressonância Magnética , Exame Neurológico , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
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