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[PMID]:26431331
[Au] Autor:Ali R; Apte S; Vilalta M; Subbarayan M; Miao Z; Chin FT; Graves EE
[Ad] Endereço:Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.
[Ti] Título:18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models.
[So] Source:PLoS One;10(10):e0139425, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.
[Mh] Termos MeSH primário: Neoplasias Experimentais/radioterapia
Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Adenocarcinoma/diagnóstico por imagem
Adenocarcinoma/radioterapia
Animais
Carcinoma/diagnóstico por imagem
Carcinoma/radioterapia
Hipóxia Celular
Linhagem Celular Tumoral
Fracionamento de Dose
Etanidazol/análogos & derivados
Etanidazol/análise
Radioisótopos de Flúor/análise
Xenoenxertos
Seres Humanos
Hidrocarbonetos Fluorados/análise
Masculino
Camundongos
Camundongos Nus
Neoplasias Experimentais/diagnóstico por imagem
Dosagem Radioterapêutica
Tela Subcutânea
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151003
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0139425


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[PMID]:25832683
[Au] Autor:Aguilera TA; Giaccia AJ
[Ad] Endereço:Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, California.
[Ti] Título:The end of the hypoxic EPOch.
[So] Source:Int J Radiat Oncol Biol Phys;91(5):895-7, 2015 Apr 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/radioterapia
Hipóxia Celular/efeitos dos fármacos
Eritropoetina/efeitos adversos
Neoplasias de Cabeça e Pescoço/radioterapia
Radiossensibilizantes/efeitos adversos
Neoplasias do Colo do Útero/radioterapia
[Mh] Termos MeSH secundário: Anemia/complicações
Anemia/terapia
Transfusão de Sangue
Hipóxia Celular/fisiologia
Ensaios Clínicos como Assunto
Etanidazol/uso terapêutico
Feminino
Seres Humanos
Masculino
Misonidazol/uso terapêutico
Radiossensibilizantes/uso terapêutico
Receptores da Eritropoetina/metabolismo
Falha de Tratamento
[Pt] Tipo de publicação:EDITORIAL
[Nm] Nome de substância:
0 (Radiation-Sensitizing Agents); 0 (Receptors, Erythropoietin); 11096-26-7 (Erythropoietin); 30DKA3Q1HL (Etanidazole); 8FE7LTN8XE (Misonidazole)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:150402
[Lr] Data última revisão:
150402
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150403
[St] Status:MEDLINE


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[PMID]:25745093
[Au] Autor:Koch CJ; Evans SM
[Ad] Endereço:University of Pennsylvania Medical Center 195 John Morgan Building Philadelphia, PA 19104 E-mail: kochc@mail.med.upenn.edu.
[Ti] Título:Pharmacokinetic and pharmacodynamic modifiers of EF5 uptake and binding.
[So] Source:J Nucl Med;56(4):653, 2015 Apr.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Transformação Celular Neoplásica
Etanidazol/análogos & derivados
Radioisótopos de Flúor
Hidrocarbonetos Fluorados/metabolismo
Neoplasias/metabolismo
Neoplasias/patologia
Tomografia por Emissão de Pósitrons
[Mh] Termos MeSH secundário: Animais
Seres Humanos
[Pt] Tipo de publicação:COMMENT; LETTER
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 30DKA3Q1HL (Etanidazole)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150307
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.114.151662


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[PMID]:25745087
[Au] Autor:Chitneni SK; Bida GT; Zalutsky MR; Dewhirst MW
[Ad] Endereço:Duke University Medical Center Box 3808Durham, NC 27710 E-mail: satish.chitneni@duke.edu.
[Ti] Título:Reply: Pharmacokinetic and Pharmacodynamic Modifiers of EF5 Uptake and Binding.
[So] Source:J Nucl Med;56(4):653-4, 2015 Apr.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Transformação Celular Neoplásica
Etanidazol/análogos & derivados
Radioisótopos de Flúor
Hidrocarbonetos Fluorados/metabolismo
Neoplasias/metabolismo
Neoplasias/patologia
Tomografia por Emissão de Pósitrons
[Mh] Termos MeSH secundário: Animais
Seres Humanos
[Pt] Tipo de publicação:COMMENT; LETTER
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 30DKA3Q1HL (Etanidazole)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:151119
[Lr] Data última revisão:
151119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150307
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.115.154054


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[PMID]:24898846
[Au] Autor:Komar G; Lehtiö K; Seppänen M; Eskola O; Levola H; Lindholm P; Sipilä H; Seppälä J; Grénman R; Solin O; Minn H
[Ad] Endereço:Turku PET Centre, Kiinamyllynkatu 4-8, 20521, Turku, Finland, gaber.komar@utu.fi.
[Ti] Título:Prognostic value of tumour blood flow, [¹8F]EF5 and [¹8F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy.
[So] Source:Eur J Nucl Med Mol Imaging;41(11):2042-50, 2014 Nov.
[Is] ISSN:1619-7089
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [(18)F]FDG, a new hypoxia tracer [(18)F]EF5 and the perfusion tracer [(15)O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. METHODS: The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [(15)O]H2O PET images using a one-tissue compartment model. [(18)F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [(18)F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. RESULTS: Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [(18)F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [(18)F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [(18)F]FDG SUVmax, [(18)F]EF5 T/M ratio and blood flow. CONCLUSION: Our study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [(18)F]EF5 showed a stronger correlation with a poor clinical outcome than [(18)F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [(18)F]EF5 may act as a surrogate marker of radioresistance.
[Mh] Termos MeSH primário: Quimiorradioterapia
Etanidazol/análogos & derivados
Fluordesoxiglucose F18
Neoplasias de Cabeça e Pescoço/irrigação sanguínea
Neoplasias de Cabeça e Pescoço/diagnóstico
Hidrocarbonetos Fluorados
Tomografia por Emissão de Pósitrons
Tomografia Computadorizada por Raios X
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Neoplasias de Cabeça e Pescoço/terapia
Seres Humanos
Masculino
Meia-Idade
Imagem Multimodal
Prognóstico
Análise de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Hydrocarbons, Fluorinated); 0Z5B2CJX4D (Fluorodeoxyglucose F18); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide)
[Em] Mês de entrada:1506
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140606
[St] Status:MEDLINE
[do] DOI:10.1007/s00259-014-2818-3


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[PMID]:24854792
[Au] Autor:Chitneni SK; Bida GT; Zalutsky MR; Dewhirst MW
[Ad] Endereço:Department of Radiology, Duke University Medical Center, Durham, North Carolina; and satish.chitneni@duke.edu.
[Ti] Título:Comparison of the Hypoxia PET Tracer (18)F-EF5 to Immunohistochemical Marker EF5 in 3 Different Human Tumor Xenograft Models.
[So] Source:J Nucl Med;55(7):1192-7, 2014 Jul.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The availability of (18)F-labeled and unlabeled 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) allows for a comparative assessment of tumor hypoxia by PET and immunohistochemistry; however, the combined use of these 2 approaches has not been fully assessed in vivo. The aim of this study was to evaluate (18)F-EF5 tumor uptake versus EF5 binding and hypoxia as determined from immunohistochemistry at both macroscopic and microregional levels. METHODS: Three tumor models-PC3, HCT116, and H460-were evaluated. Tumor-bearing animals were coinjected with (18)F-EF5 and EF5 (30 mg/kg), and PET imaging was performed at 2.5 h after injection. After PET imaging and 2 min after Hoechst 33342 injection, the tumors were excised and evaluated for (18)F-EF5 distribution by autoradiography and EF5 binding by immunohistochemistry. Additionally, the effects of nonradioactive EF5 (30 mg/kg) on the hypoxia-imaging characteristics of (18)F-EF5 were evaluated by comparing the PET data for H460 tumors with those from animals injected with (18)F-EF5 alone. RESULTS: The uptake of (18)F-EF5 in hypoxic tumor regions and the spatial relationship between (18)F-EF5 uptake and EF5 binding varied among tumors. H460 tumors showed higher tumor-to-muscle contrast in PET imaging; however, the distribution and uptake of the tracer was less specific for hypoxia in H460 than in HCT116 and PC3 tumors. Correlation analyses revealed that the highest spatial correlation between (18)F-EF5 uptake and EF5 binding was in PC3 tumors (r = 0.73 ± 0.02) followed by HCT116 (r = 0.60 ± 0.06) and H460 (r = 0.53 ± 0.10). Uptake and binding of (18)F-EF5 and EF5 correlated negatively with Hoechst 33342 perfusion marker distribution in the 3 tumor models. Image contrast and heterogeneous uptake of (18)F-EF5 in H460 tumors was significantly higher when the radiotracer was used alone versus in combination with unlabeled EF5 (tumor-to-muscle ratio of 2.51 ± 0.33 vs. 1.71 ± 0.17, P < 0.001). CONCLUSION: The uptake and hypoxia selectivity of (18)F-EF5 varied among tumor models when animals also received nonradioactive EF5. Combined use of radioactive and nonradioactive EF5 for independent assessment of tumor hypoxia by PET and immunohistochemistry methods is promising; however, the EF5 drug concentrations that are required for immunohistochemistry assays may affect the uptake of (18)F-EF5 in hypoxic cells in certain tumor types as observed in H460 in this study.
[Mh] Termos MeSH primário: Transformação Celular Neoplásica
Etanidazol/análogos & derivados
Radioisótopos de Flúor
Hidrocarbonetos Fluorados/metabolismo
Neoplasias/metabolismo
Neoplasias/patologia
Tomografia por Emissão de Pósitrons
[Mh] Termos MeSH secundário: Animais
Benzimidazóis/metabolismo
Transporte Biológico
Hipóxia Celular
Linhagem Celular Tumoral
Etanidazol/metabolismo
Seres Humanos
Imuno-Histoquímica
Camundongos
Neoplasias/diagnóstico por imagem
Ratos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Benzimidazoles); 0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide); P976261J69 (bisbenzimide ethoxide trihydrochloride)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140524
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.114.137448


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[PMID]:23982250
[Au] Autor:Speicher PJ; Beasley GM; Jiang B; Lidsky ME; Palmer GM; Scarbrough PM; Mosca PJ; Dewhirst MW; Tyler DS
[Ad] Endereço:Department of Surgery, Duke University Medical Center, Durham, NC, USA, paul.speicher@duke.edu.
[Ti] Título:Hypoxia in melanoma: using optical spectroscopy and EF5 to assess tumor oxygenation before and during regional chemotherapy for melanoma.
[So] Source:Ann Surg Oncol;21(5):1435-40, 2014 May.
[Is] ISSN:1534-4681
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: There is increasing evidence that tumor hypoxia plays a significant role in the chemoresistance of melanoma, but to our knowledge, real-time tumor oxygenation during isolated limb infusion (ILI) has not been studied. We sought to demonstrate the feasibility of measuring real-time alterations in tissue oxygenation. METHODS: Consecutive patients with histologically confirmed in-transit melanoma were enrolled onto a prospective single-arm pilot study and administered the hypoxia marker drug EF5. All patients were treated with ILI. Optical spectroscopy readings were obtained at three locations: two discrete target lesions and one normal skin control. Measurements were taken at 11 predefined time points during ILI. RESULTS: A total of six patients were enrolled onto this pilot study. Intratumor and normal skin optical spectroscopy readings were found to have discrete inflection points throughout the duration of therapy, corresponding with established time points. Baseline hypoxia as measured by both optical spectroscopy and EF5 immunofluorescence was variable, but on the basis of optical spectra, tumors appeared to become more hypoxic compared to normal skin after tourniquet application. The optical hypoxia signature was variable between patients while hemoglobin absorption increased. CONCLUSIONS: To our knowledge, this is the first use of real-time optical spectroscopy to evaluate oxygenation and perfusion within melanoma lesions during regional chemotherapy. We report our development of this new noninvasive means of assessing tumor vascular function, which has the potential to be a powerful tool for noninvasive examination of the melanoma tumor microenvironment.
[Mh] Termos MeSH primário: Etanidazol/análogos & derivados
Hidrocarbonetos Fluorados
Hipóxia/diagnóstico
Indicadores e Reagentes
Melanoma/patologia
[Mh] Termos MeSH secundário: Idoso
Antineoplásicos Alquilantes/administração & dosagem
Estudos de Viabilidade
Feminino
Seguimentos
Seres Humanos
Hipóxia/metabolismo
Masculino
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Melfalan/administração & dosagem
Meia-Idade
Estadiamento de Neoplasias
Projetos Piloto
Prognóstico
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Alkylating); 0 (Hydrocarbons, Fluorinated); 0 (Indicators and Reagents); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide); Q41OR9510P (Melphalan)
[Em] Mês de entrada:1412
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130829
[St] Status:MEDLINE
[do] DOI:10.1245/s10434-013-3222-0


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[PMID]:23740105
[Au] Autor:Chitneni SK; Bida GT; Yuan H; Palmer GM; Hay MP; Melcher T; Wilson WR; Zalutsky MR; Dewhirst MW
[Ad] Endereço:Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA. satish.chitneni@duke.edu
[Ti] Título:18F-EF5 PET imaging as an early response biomarker for the hypoxia-activated prodrug SN30000 combined with radiation treatment in a non-small cell lung cancer xenograft model.
[So] Source:J Nucl Med;54(8):1339-46, 2013 Aug.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: Hypoxia is a significant therapeutic problem for solid tumors because hypoxic cells are treatment-resistant and more aggressive. Hypoxia-activated prodrugs such as SN30000 use a mechanism of activation in hypoxic cells similar to that of 2-nitroimidazole hypoxia PET tracers. Therefore, we have evaluated the usefulness of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-(18)F-pentafluoropropyl)-acetamide ((18)F-EF5) PET to monitor and predict tumor response to SN30000 plus radiation treatment (RT). METHODS: Human non-small cell lung cancer xenografts (H460) in athymic rats were imaged with (18)F-EF5 PET before and after treatment with SN30000 (90 mg/kg), with or without 15-Gy RT. The feasibility of imaging early changes in hypoxia in response to SN30000 was examined 24 h after treatment, followed by ex vivo γ-counting and immunohistochemical examination to study drug-induced apoptosis. Subsequently, the therapeutic effects of SN30000 with or without RT were evaluated in tumor growth delay studies and compared with early treatment-induced changes observed by (18)F-EF5 PET. Changes in tumor hemoglobin oxygen saturation as a function of time after treatment measured by optical spectroscopy were compared with PET data. RESULTS: The uptake of (18)F-EF5 was significantly lower in SN30000-treated tumors than in saline controls 24 h after treatment (mean standardized uptake value, 0.44 ± 0.08 vs. 0.56 ± 0.08 for control group; P < 0.05). Apoptosis was significantly higher in SN30000-treated tumors than in controls. Early treatment-induced changes in (18)F-EF5 uptake were indicative of tumor response in growth delay studies at the group level. SN30000 plus RT significantly decreased (18)F-EF5 uptake relative to baseline and resulted in complete tumor remission in 5 of 7 animals. SN30000 alone decreased (18)F-EF5 uptake, generally in tumors with high initial standardized uptake values, and showed a minor tumor growth delay effect. The changes induced by SN30000 with or without RT in (18)F-EF5 uptake correlated with baseline hypoxia levels. RT caused significant increases in tumor oxygen concentration and hemoglobin oxygen saturation. CONCLUSION: A hypoxia PET imaging agent can measure changes in tumor hypoxic fraction in response to SN30000. These results suggest the utility of (18)F-EF5 PET for monitoring early response to tumor treatment with SN30000 plus RT in the clinical development of this novel hypoxia-activated prodrug.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem
Transformação Celular Neoplásica
Óxidos N-Cíclicos/uso terapêutico
Etanidazol/análogos & derivados
Radioisótopos de Flúor
Hidrocarbonetos Fluorados
Neoplasias Pulmonares/diagnóstico por imagem
Tomografia por Emissão de Pósitrons
Triazinas/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma Pulmonar de Células não Pequenas/patologia
Carcinoma Pulmonar de Células não Pequenas/radioterapia
Hipóxia Celular/efeitos dos fármacos
Hipóxia Celular/efeitos da radiação
Proliferação Celular/efeitos dos fármacos
Proliferação Celular/efeitos da radiação
Óxidos N-Cíclicos/farmacologia
Feminino
Seres Humanos
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/patologia
Neoplasias Pulmonares/radioterapia
Pró-Fármacos/farmacologia
Pró-Fármacos/uso terapêutico
Ratos
Resultado do Tratamento
Triazinas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CEN-209); 0 (Cyclic N-Oxides); 0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 0 (Prodrugs); 0 (Triazines); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide)
[Em] Mês de entrada:1310
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130607
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.112.116293


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[PMID]:22869463
[Au] Autor:Kirjavainen A; Forsback S; Grönroos TJ; Haavisto L; Haaparanta M; Solin O
[Ad] Endereço:Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, University of Turku, Turku, Finland.
[Ti] Título:Electrophilic addition of chlorine monofluoride for PET tracers.
[So] Source:Mol Imaging Biol;15(2):131-5, 2013 Apr.
[Is] ISSN:1860-2002
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: We have studied the utility of [(18)F]ClF electrophilic addition to the carbon-carbon double bond of analogues of a model positron emission tomography (PET) tracer, [(18)F]EF5. The consequence of simultaneous chlorine/fluorine addition on lipophilicity and biological activity of the molecule is evaluated. PROCEDURES: Post-target produced [(18)F]F2 was reacted with Cl2 to produce [(18)F]ClF, which was used in electrophilic addition. RESULTS: [(18)F]ClF was produced and used to label chlorinated analogues of [(18)F]EF5. The chlorinated analogues, [(18)F]EF4Cla and [(18)F]EF4Clb, were synthesized simultaneously. The in vivo uptake of the analogues compared well with [(18)F]EF5 uptake in tumor-bearing mice. CONCLUSION: [(18)F]ClF is a suitable labeling reagent for electrophilic addition to double bonds of PET tracers. The results show that the modification of the pentafluoro group of [(18)F]EF5 by monofluorine-for-chlorine exchange affected the lipophilicity, but the hypoxia avidity of these molecules was not apparently altered.
[Mh] Termos MeSH primário: Cloretos/química
Fluoretos/química
Tomografia por Emissão de Pósitrons/métodos
Compostos Radiofarmacêuticos/química
[Mh] Termos MeSH secundário: Animais
Cloretos/farmacocinética
Etanidazol/análogos & derivados
Etanidazol/química
Etanidazol/farmacocinética
Fluoretos/farmacocinética
Hidrocarbonetos Fluorados/química
Hidrocarbonetos Fluorados/farmacocinética
Masculino
Camundongos
Camundongos Nus
Neoplasias Experimentais/diagnóstico por imagem
Neoplasias Experimentais/metabolismo
Compostos Radiofarmacêuticos/síntese química
Compostos Radiofarmacêuticos/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chlorides); 0 (Hydrocarbons, Fluorinated); 0 (Radiopharmaceuticals); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide); Q80VPU408O (Fluorides)
[Em] Mês de entrada:1311
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120808
[St] Status:MEDLINE
[do] DOI:10.1007/s11307-012-0584-9


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[PMID]:22897720
[Au] Autor:Lin LL; Silvoniemi A; Stubbs JB; Rengan R; Suilamo S; Solin O; Divgi C; Eskola O; Sorger JM; Stabin MG; Kachur A; Hahn SM; Grönroos TJ; Forsback S; Evans SM; Koch CJ; Minn H
[Ad] Endereço:Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Radiation dosimetry and biodistribution of the hypoxia tracer (18)F-EF5 in oncologic patients.
[So] Source:Cancer Biother Radiopharm;27(7):412-9, 2012 Sep.
[Is] ISSN:1557-8852
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: The primary goals of this study were to determine the biodistribution and excretion of (18)F-EF5 in oncologic patients, to estimate the radiation-absorbed dose and to determine the safety of this drug. METHODS: Sixteen patients with histologically confirmed malignancy received a mean intravenous infusion of 217 MBq (range 107-364 MBq) of (18)F-EF5. Over a 4-6-hour period, four to five serial positron emission tomography (PET) or PET/computed tomography (CT) scans were obtained. To calculate the radiation dosimetry estimates, volumes of interest were drawn over the source organs for each PET scan or on the CT for each PET/CT scan. Serial blood samples were obtained to measure (18)F-EF5 blood clearance. Bladder-wall dose was calculated based on urine activity measurements. RESULTS: The urinary bladder received the largest radiation-absorbed dose, 0.12 ± 0.034 mSv/MBq (mean ± SD). The average effective dose equivalent and the effective dose of (18)F-EF5 were 0.021 ± 0.003 mSv/MBq and 0.018 ± 0.002 mSv/MBq, respectively. (18)F-EF5 was well tolerated in all subjects. CONCLUSIONS: (18)F-EF5 was demonstrated to be safe for patients, and the radiation exposure is clinically acceptable. As with any radiotracer with primary excretion in the urine, the bladder-wall dose can be minimized by active hydration and frequent voiding.
[Mh] Termos MeSH primário: Etanidazol/análogos & derivados
Radioisótopos de Flúor
Hidrocarbonetos Fluorados/farmacocinética
Neoplasias/diagnóstico por imagem
Neoplasias/metabolismo
Compostos Radiofarmacêuticos/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Hipóxia Celular/fisiologia
Relação Dose-Resposta à Radiação
Etanidazol/farmacocinética
Etanidazol/urina
Feminino
Radioisótopos de Flúor/química
Seres Humanos
Hidrocarbonetos Fluorados/urina
Masculino
Meia-Idade
Neoplasias/urina
Tomografia por Emissão de Pósitrons
Dose de Radiação
Radiometria/métodos
Compostos Radiofarmacêuticos/urina
Distribuição Tecidual
Bexiga Urinária/metabolismo
Bexiga Urinária/efeitos da radiação
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Fluorine Radioisotopes); 0 (Hydrocarbons, Fluorinated); 0 (Radiopharmaceuticals); 30DKA3Q1HL (Etanidazole); 383HJ2T87O (2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide)
[Em] Mês de entrada:1304
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120818
[St] Status:MEDLINE
[do] DOI:10.1089/cbr.2011.1130



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