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[PMID]:28596159
[Au] Autor:da Ponte KF; Berro DH; Collet S; Constans JM; Emery E; Valable S; Guillamo JS
[Ad] Endereço:Normandie University, UNICAEN, CEA, CNRS, ISTCT/CERVOxy Group, Caen, France.
[Ti] Título:In Vivo Relationship Between Hypoxia and Angiogenesis in Human Glioblastoma: A Multimodal Imaging Study.
[So] Source:J Nucl Med;58(10):1574-1579, 2017 Oct.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. This aggressiveness is in part attributed to the closely interrelated phenomena tumor hypoxia and angiogenesis, although few in vivo data exist in human brain tumors. This work aimed to study hypoxia and angiogenesis, in vivo and in situ, in patients admitted with GBM using multimodal imaging. Twenty-three GBM patients were assessed by F-fluoromisonidazole ( F-FMISO) PET and conventional and perfusion MRI before surgery. The level and location of hypoxia ( F-FMISO uptake, evaluated by tumor-to-blood [T/B] ratio), vascularization (cerebral blood volume [CBV]), and vascular permeability (contrast enhancement after gadolinium injection) were analyzed. The spatial relationship between tumor hypoxia and angiogenesis was assessed by an overlap analysis of the volume of F-FMISO uptake and the volumes of the high CBV regions and the contrast-enhancement regions. A significant correlation was found between hypoxia and hypervascularization, especially for their maximum values (volume of maximal tumor hypoxia vs. relative CBV: = 0.61, = 0.002) and their volumes (hypoxia vs. hypervascularization: = 0.91, < 0.001). A large proportion of the high CBVs collocated with hypoxia (81.3%) and with contrast enhancement (46.5%). These results support the hypothesis of a tight association between hypoxia and angiogenesis. Our results suggest that there is insufficient tumor oxygenation in human GBM, despite increased tumor vascularization.
[Mh] Termos MeSH primário: Neoplasias Encefálicas/diagnóstico por imagem
Glioblastoma/diagnóstico por imagem
Imagem Multimodal
Neovascularização Patológica
Hipóxia Tumoral
[Mh] Termos MeSH secundário: Adulto
Idoso
Neoplasias Encefálicas/irrigação sanguínea
Neoplasias Encefálicas/patologia
Feminino
Glioblastoma/irrigação sanguínea
Glioblastoma/patologia
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Misonidazol/análogos & derivados
Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170610
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.188557


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[PMID]:28540739
[Au] Autor:Grimes DR; Warren DR; Warren S
[Ad] Endereço:1 Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratory, University of Oxford, Old Road Campus Research Building, Off Roosevelt Drive, Oxford OX37DQ, UK.
[Ti] Título:Hypoxia imaging and radiotherapy: bridging the resolution gap.
[So] Source:Br J Radiol;90(1076):20160939, 2017 Aug.
[Is] ISSN:1748-880X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Oxygen distribution is a major determinant of treatment success in radiotherapy, with well-oxygenated tumour regions responding by up to a factor of three relative to anoxic volumes. Conversely, tumour hypoxia is associated with treatment resistance and negative prognosis. Tumour oxygenation is highly heterogeneous and difficult to measure directly. The recent advent of functional hypoxia imaging modalities such as fluorine-18 fluoromisonidazole positron emission tomography have shown promise in non-invasively determining regions of low oxygen tension. This raises the prospect of selectively increasing dose to hypoxic subvolumes, a concept known as dose painting. Yet while this is a promising approach, oxygen-mediated radioresistance is inherently a multiscale problem, and there are still a number of substantial challenges that must be overcome if hypoxia dose painting is to be successfully implemented. Current imaging modalities are limited by the physics of such systems to have resolutions in the millimetre regime, whereas oxygen distribution varies over a micron scale, and treatment delivery is typically modulated on a centimetre scale. In this review, we examine the mechanistic basis and implications of the radiobiological oxygen effect, the factors influencing microscopic heterogeneity in tumour oxygenation and the consequent challenges in the interpretation of clinical hypoxia imaging (in particular fluorine-18 fluoromisonidazole positron emission tomography). We also discuss dose-painting approaches and outline challenges that must be addressed to improve this treatment paradigm.
[Mh] Termos MeSH primário: Hipóxia/fisiopatologia
Misonidazol/análogos & derivados
Neoplasias/diagnóstico por imagem
Neoplasias/radioterapia
Tomografia por Emissão de Pósitrons
Radiossensibilizantes
[Mh] Termos MeSH secundário: Hipóxia Celular
Seres Humanos
Dosagem Radioterapêutica
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Radiation-Sensitizing Agents); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1259/bjr.20160939


  3 / 1475 MEDLINE  
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[PMID]:28360207
[Au] Autor:Grkovski M; Emmas SA; Carlin SD
[Ad] Endereço:Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
[Ti] Título:F-Fluoromisonidazole Kinetic Modeling for Characterization of Tumor Perfusion and Hypoxia in Response to Antiangiogenic Therapy.
[So] Source:J Nucl Med;58(10):1567-1573, 2017 Oct.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiparametric imaging of tumor perfusion and hypoxia with dynamic F-fluoromisonidazole ( F-FMISO) PET may allow for an improved response assessment to antiangiogenic therapies. Cediranib (AZD2171) is a potent inhibitor of tyrosine kinase activity associated with vascular endothelial growth factor receptors 1, 2, and 3, currently in phase II/III clinical trials. Serial dynamic F-FMISO PET was performed to investigate changes in tumor biomarkers of perfusion and hypoxia after cediranib treatment. Twenty-one rats bearing HT29 colorectal xenograft tumors were randomized into a vehicle-treated control group (0.5% methylcellulose daily for 2 d [5 rats] or 7 d [4 rats]) and a cediranib-treated test group (3 mg/kg daily for 2 or 7 d; 6 rats in both groups). All rats were imaged before and after treatment, using a 90-min dynamic PET acquisition after administration of 42.1 ± 3.9 MBq of F-FMISO by tail vein injection. Tumor volumes were delineated manually, and the input function was image-derived (abdominal aorta). Kinetic modeling was performed using an irreversible 1-plasma 2-tissue compartmental model to estimate the kinetic rate constants , / , and -surrogates for perfusion, F-FMISO distribution volume, and hypoxia-mediated entrapment, respectively. Tumor-to-blood ratios (TBRs) were calculated on the last dynamic frame (80-90 min). Tumors were assessed ex vivo by digital autoradiography and immunofluorescence for microscopic visualization of perfusion (pimonidazole) and hypoxia (Hoechst 33342). Cediranib treatment resulted in significant reduction of mean voxelwise F-FMISO TBR, , and / in both the 2-d and the 7-d groups ( < 0.05). The parameter was increased in both groups but reached significance only in the 2-d group. In the vehicle-treated groups, no significant change in TBR, , / , or was observed ( > 0.2). Ex vivo tumor analysis confirmed the presence of hypoxic tumor regions that nevertheless exhibited relatively lower F-FMISO uptake. F-FMISO kinetic modeling reveals a more detailed response to antiangiogenic treatment than a single static image is able to reveal. The reduced mean reflects a reduction in tumor vascular perfusion, whereas the increased reflects a rise in hypoxia-mediated entrapment of the radiotracer. However, if only late static images are analyzed, the observed reduction in F-FMISO uptake after treatment with cediranib may be mistakenly interpreted as a global decrease, rather than an increase, in tumor hypoxia. These findings support the use of F-FMISO kinetic modeling to more accurately characterize the response to treatments that have a direct effect on tumor vascularization and perfusion.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/farmacologia
Circulação Sanguínea/efeitos dos fármacos
Neoplasias Colorretais/tratamento farmacológico
Misonidazol/análogos & derivados
Modelos Biológicos
Quinazolinas/farmacologia
Hipóxia Tumoral/efeitos dos fármacos
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/uso terapêutico
Animais
Transformação Celular Neoplásica
Neoplasias Colorretais/irrigação sanguínea
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Feminino
Células HT29
Seres Humanos
Cinética
Misonidazol/metabolismo
Tomografia por Emissão de Pósitrons
Quinazolinas/uso terapêutico
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Quinazolines); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole); NQU9IPY4K9 (cediranib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.117.190892


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[PMID]:28301873
[Au] Autor:Bueno MJ; Mouron S; Quintela-Fandino M
[Ad] Endereço:Breast Cancer Clinical Research Unit, CNIO-Spanish National Research Cancer Centre, Madrid, Spain.
[Ti] Título:Personalising and targeting antiangiogenic resistance: a complex and multifactorial approach.
[So] Source:Br J Cancer;116(9):1119-1125, 2017 Apr 25.
[Is] ISSN:1532-1827
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pathological angiogenesis involves complex and dynamic interactions between tumour cells and other lineages existing in the microenvironment of the tumour. Preclinical and clinical data suggest that tumours can show dual, different adaptive responses against antiangiogenic agents: one successful adaptation is vascular normalisation, whereas the second adaptation is elicited through vascular trimming and increased hypoxia. These phenomena depend on the type of tumour and the type of agent. The classical approach for investigating acquired resistance against antiangiogenic agents is to identify compensatory signalling pathways emerging in response to VEGF blockade, which has led to the development of highly effective drugs; however, ultimately these drugs fail. Here we review how the dual stromal adaptive patterns determine the mechanisms of escape that go beyond the reprogramming of signal transduction pathways, which obliges us to investigate the tumour as an ecosystem and to develop uni- and multicompartmental models that explain drug resistance involving metabolic and immune reprogramming. We also propose a method for facilitating personalised therapeutic decisions, which uses 18F-fluoromisonidazole-positron emission tomography to monitor the dual stromal response in tumours of individual patients.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/uso terapêutico
Resistência a Medicamentos Antineoplásicos/genética
Neovascularização Patológica/tratamento farmacológico
Medicina de Precisão
[Mh] Termos MeSH secundário: Hipóxia Celular/efeitos dos fármacos
Seres Humanos
Misonidazol/análogos & derivados
Misonidazol/uso terapêutico
Neovascularização Patológica/genética
Células Estromais/efeitos dos fármacos
Células Estromais/patologia
Microambiente Tumoral/efeitos dos fármacos
Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (VEGFA protein, human); 0 (Vascular Endothelial Growth Factor A); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170317
[St] Status:MEDLINE
[do] DOI:10.1038/bjc.2017.69


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[PMID]:28254869
[Au] Autor:Vera P; Thureau S; Chaumet-Riffaud P; Modzelewski R; Bohn P; Vermandel M; Hapdey S; Pallardy A; Mahé MA; Lacombe M; Boisselier P; Guillemard S; Olivier P; Beckendorf V; Salem N; Charrier N; Chajon E; Devillers A; Aide N; Danhier S; Denis F; Muratet JP; Martin E; Riedinger AB; Kolesnikov-Gauthier H; Dansin E; Massabeau C; Courbon F; Farcy Jacquet MP; Kotzki PO; Houzard C; Mornex F; Vervueren L; Paumier A; Fernandez P; Salaun M; Dubray B
[Ad] Endereço:Department of Nuclear Medicine, Henri Becquerel Cancer Center and Rouen University Hospital & QuantIF-LITIS, University of Rouen, Rouen, France pierre.vera@chb.unicancer.fr.
[Ti] Título:Phase II Study of a Radiotherapy Total Dose Increase in Hypoxic Lesions Identified by F-Misonidazole PET/CT in Patients with Non-Small Cell Lung Carcinoma (RTEP5 Study).
[So] Source:J Nucl Med;58(7):1045-1053, 2017 Jul.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant F-misonidazole ( F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-ß = 0.95). Seventy-nine patients were preincluded, 54 were included, and 34 were F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the F-FMISO-negative patients ( = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Our approach results in a response rate of 40% or more, with acceptable toxicity. F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Carcinoma Pulmonar de Células não Pequenas/radioterapia
Fracionamento de Dose
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/radioterapia
Misonidazol/análogos & derivados
[Mh] Termos MeSH secundário: Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem
Feminino
França
Seres Humanos
Neoplasias Pulmonares/diagnóstico por imagem
Masculino
Meia-Idade
Misonidazol/farmacocinética
Variações Dependentes do Observador
Compostos Radiofarmacêuticos/farmacocinética
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Taxa de Sobrevida
Resultado do Tratamento
Hipóxia Tumoral/efeitos da radiação
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.188367


  6 / 1475 MEDLINE  
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[PMID]:28232611
[Au] Autor:Schwartz J; Grkovski M; Rimner A; Schöder H; Zanzonico PB; Carlin SD; Staton KD; Humm JL; Nehmeh SA
[Ad] Endereço:Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York schwarj1@mkscc.org.
[Ti] Título:Pharmacokinetic Analysis of Dynamic F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.
[So] Source:J Nucl Med;58(6):911-919, 2017 Jun.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. F-fluoromisonidazole ( F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static F-FDG and a dynamic F-FMISO scan lasting 168 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. We derived average values of F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate ( ) and delivery rate ( ), influx rate ( ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, and had a significant strong correlation for all tissue types. The TBR- correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, - voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R -0.23 0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R 0.5). All lesions showed distinct F-FMISO uptake. Variable F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constant Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzero values.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/metabolismo
Neoplasias Pulmonares/metabolismo
Misonidazol/análogos & derivados
Modelos Biológicos
Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem
Simulação por Computador
Feminino
Seres Humanos
Neoplasias Pulmonares/diagnóstico por imagem
Masculino
Taxa de Depuração Metabólica
Meia-Idade
Misonidazol/farmacocinética
Compostos Radiofarmacêuticos/farmacocinética
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Distribuição Tecidual
[Pt] Tipo de publicação:CLINICAL TRIAL; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170225
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.180422


  7 / 1475 MEDLINE  
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[PMID]:28183993
[Au] Autor:Grkovski M; Schöder H; Lee NY; Carlin SD; Beattie BJ; Riaz N; Leeman JE; O'Donoghue JA; Humm JL
[Ad] Endereço:Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York grkovskm@mkscc.org.
[Ti] Título:Multiparametric Imaging of Tumor Hypoxia and Perfusion with F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer.
[So] Source:J Nucl Med;58(7):1072-1080, 2017 Jul.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with F-fluoromisonidazole ( F-FMISO) dynamic PET (dPET) in head and neck cancer. One hundred twenty head and neck cancer patients underwent 0- to 30-min F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection. A total of 248 lesions (≥2 cm ) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible 1-plasma 2-tissue-compartment model to calculate surrogate biomarkers of tumor hypoxia ( ), perfusion ( ), and F-FMISO distribution volume. The analysis was repeated with truncated dPET datasets. Substantial inter- and intratumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound F-FMISO was rapid in all tumors. F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy between maps and total F-FMISO uptake and reducing the dynamic range of total F-FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from a truncated 20-min dataset. F-FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion, and radiotracer distribution volume. These data clarify the ambiguity in interpreting F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of F-FMISO dPET into the clinic.
[Mh] Termos MeSH primário: Neoplasias de Cabeça e Pescoço/diagnóstico
Neoplasias de Cabeça e Pescoço/metabolismo
Misonidazol/análogos & derivados
Neovascularização Patológica/diagnóstico
Neovascularização Patológica/metabolismo
Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Neoplasias de Cabeça e Pescoço/irrigação sanguínea
Seres Humanos
Interpretação de Imagem Assistida por Computador/métodos
Masculino
Meia-Idade
Misonidazol/farmacocinética
Imagem Multimodal/métodos
Neovascularização Patológica/sangue
Variações Dependentes do Observador
Oxigênio/metabolismo
Imagem de Perfusão/métodos
Compostos Radiofarmacêuticos/farmacocinética
Reprodutibilidade dos Testes
Estudos Retrospectivos
Sensibilidade e Especificidade
Hipóxia Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Radiopharmaceuticals); 082285VIDF (fluoromisonidazole); 8FE7LTN8XE (Misonidazole); S88TT14065 (Oxygen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.188649


  8 / 1475 MEDLINE  
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[PMID]:28183987
[Au] Autor:Fuchs K; Kuehn A; Mahling M; Guenthoer P; Hector A; Schwenck J; Hartl D; Laufer S; Kohlhofer U; Quintanilla-Martinez L; Reischl G; Röcken M; Pichler BJ; Kneilling M
[Ad] Endereço:Department of Preclinical Imaging and Radiopharmacy, Werner Siemens Imaging Center, Eberhard Karls University Tuebingen, Tuebingen, Germany.
[Ti] Título:In Vivo Hypoxia PET Imaging Quantifies the Severity of Arthritic Joint Inflammation in Line with Overexpression of Hypoxia-Inducible Factor and Enhanced Reactive Oxygen Species Generation.
[So] Source:J Nucl Med;58(5):853-860, 2017 May.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypoxia is essential for the development of autoimmune diseases such as rheumatoid arthritis (RA) and is associated with the expression of reactive oxygen species (ROS), because of the enhanced infiltration of immune cells. The aim of this study was to demonstrate the feasibility of measuring hypoxia noninvasively in vivo in arthritic ankles with PET/MRI using the hypoxia tracers F-fluoromisonidazole ( F-FMISO) and F-fluoroazomycinarabinoside ( F-FAZA). Additionally, we quantified the temporal dynamics of hypoxia and ROS stress using L-012, an ROS-sensitive chemiluminescence optical imaging probe, and analyzed the expression of hypoxia-inducible factors (HIFs). Mice underwent noninvasive in vivo PET/MRI to measure hypoxia or optical imaging to analyze ROS expression. Additionally, we performed ex vivo pimonidazole-/HIF-1α immunohistochemistry and HIF-1α/2α Western blot/messenger RNA analysis of inflamed and healthy ankles to confirm our in vivo results. Mice diseased from experimental RA exhibited a 3-fold enhancement in hypoxia tracer uptake, even in the early disease stages, and a 45-fold elevation in ROS expression in inflamed ankles compared with the ankles of healthy controls. We further found strong correlations of our noninvasive in vivo hypoxia PET data with pimonidazole and expression of HIF-1α in arthritic ankles. The strongest hypoxia tracer uptake was observed as soon as day 3, whereas the most pronounced ROS stress was evident on day 6 after the onset of experimental RA, indicating that tissue hypoxia can precede ROS stress in RA. Collectively, for the first time to our knowledge, we have demonstrated that the noninvasive measurement of hypoxia in inflammation using F-FAZA and F-FMISO PET imaging represents a promising new tool for uncovering and monitoring rheumatic inflammation in vivo. Further, because hypoxic inflamed tissues are associated with the overexpression of HIFs, specific inhibition of HIFs might represent a new powerful treatment strategy.
[Mh] Termos MeSH primário: Artrite Reumatoide/diagnóstico por imagem
Artrite Reumatoide/imunologia
Fator 1 Induzível por Hipóxia/imunologia
Misonidazol/análogos & derivados
Nitroimidazóis/imunologia
Tomografia por Emissão de Pósitrons/métodos
Espécies Reativas de Oxigênio/imunologia
[Mh] Termos MeSH secundário: Animais
Hipóxia Celular/imunologia
Camundongos
Misonidazol/imunologia
Imagem Molecular/métodos
Compostos Radiofarmacêuticos/imunologia
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Índice de Gravidade de Doença
Regulação para Cima/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hypoxia-Inducible Factor 1); 0 (Nitroimidazoles); 0 (Radiopharmaceuticals); 0 (Reactive Oxygen Species); 082285VIDF (fluoromisonidazole); 1QR3UU6P48 (fluoroazomycin arabinoside); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.116.185934


  9 / 1475 MEDLINE  
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[PMID]:27752745
[Au] Autor:Toyonaga T; Yamaguchi S; Hirata K; Kobayashi K; Manabe O; Watanabe S; Terasaka S; Kobayashi H; Hattori N; Shiga T; Kuge Y; Tanaka S; Ito YM; Tamaki N
[Ad] Endereço:Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
[Ti] Título:Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.
[So] Source:Eur J Nucl Med Mol Imaging;44(4):611-619, 2017 Apr.
[Is] ISSN:1619-7089
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.
[Mh] Termos MeSH primário: Glicemia/metabolismo
Neoplasias Encefálicas/diagnóstico por imagem
Glioblastoma/diagnóstico por imagem
Oxigênio/metabolismo
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
[Mh] Termos MeSH secundário: Adulto
Idoso
Neoplasias Encefálicas/metabolismo
Hipóxia Celular
Feminino
Fluordesoxiglucose F18
Glioblastoma/metabolismo
Glicólise
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Meia-Idade
Misonidazol/análogos & derivados
Compostos Radiofarmacêuticos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Radiopharmaceuticals); 082285VIDF (fluoromisonidazole); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 8FE7LTN8XE (Misonidazole); S88TT14065 (Oxygen)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170924
[Lr] Data última revisão:
170924
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161019
[St] Status:MEDLINE
[do] DOI:10.1007/s00259-016-3541-z


  10 / 1475 MEDLINE  
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[PMID]:27506906
[Au] Autor:Sorace AG; Syed AK; Barnes SL; Quarles CC; Sanchez V; Kang H; Yankeelov TE
[Ad] Endereço:Department of Internal Medicine, Dell Medical School, The University of Texas at Austin, 1912 Speedway, Austin, TX, 78712, USA. anna.sorace@austin.utexas.edu.
[Ti] Título:Quantitative [ F]FMISO PET Imaging Shows Reduction of Hypoxia Following Trastuzumab in a Murine Model of HER2+ Breast Cancer.
[So] Source:Mol Imaging Biol;19(1):130-137, 2017 Feb.
[Is] ISSN:1860-2002
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Evaluation of [ F]fluoromisonidazole ([ F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer. PROCEDURES: Mice with BT474, HER2+ tumors, were imaged with [ F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging. RESULTS: [ F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P < 0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P < 0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r = 0.85). CONCLUSIONS: [ F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.
[Mh] Termos MeSH primário: Neoplasias Mamárias Animais/tratamento farmacológico
Neoplasias Mamárias Animais/patologia
Misonidazol/análogos & derivados
Tomografia por Emissão de Pósitrons/métodos
Receptor ErbB-2/metabolismo
Trastuzumab/uso terapêutico
Hipóxia Tumoral
[Mh] Termos MeSH secundário: Animais
Biomarcadores Tumorais/metabolismo
Linhagem Celular Tumoral
Modelos Animais de Doenças
Feminino
Imunofluorescência
Misonidazol/química
Nitroimidazóis/farmacologia
Nitroimidazóis/uso terapêutico
Trastuzumab/farmacologia
Carga Tumoral
Hipóxia Tumoral/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Nitroimidazoles); 082285VIDF (fluoromisonidazole); 46JO4D76R2 (pimonidazole); 8FE7LTN8XE (Misonidazole); EC 2.7.10.1 (Receptor, ErbB-2); P188ANX8CK (Trastuzumab)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160811
[St] Status:MEDLINE
[do] DOI:10.1007/s11307-016-0994-1



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