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Pesquisa : D01.268.271.100.033 [Categoria DeCS]
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[PMID]:28408529
[Au] Autor:Kratochwil C; Bruchertseifer F; Rathke H; Bronzel M; Apostolidis C; Weichert W; Haberkorn U; Giesel FL; Morgenstern A
[Ad] Endereço:Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany clemens.kratochwil@med.uni-heidelberg.de.
[Ti] Título:Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding.
[So] Source:J Nucl Med;58(10):1624-1631, 2017 Oct.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to develop a treatment protocol for Ac-PSMA-617 α-radiation therapy in advanced-stage, metastatic castration-resistant prostate cancer patients with prostate-specific membrane antigen (PSMA)-positive tumor phenotype. A dosimetry estimate was calculated on the basis of time-activity curves derived from serially obtained Lu-PSMA-617 scans extrapolated to the physical half-life of Ac, assuming instant decay of unstable daughter nuclides. Salvage therapies empirically conducted with 50 ( = 4), 100 ( = 4), 150 ( = 2), and 200 kBq/kg ( = 4) of Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response. Eight of 14 patients received further cycles in either 2- or 4-mo intervals with identical or deescalated activities. Dosimetry estimates for 1 MBq of Ac-PSMA-617 assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed of 99.4% α, 0.5% ß, and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate-specific antigen decline was less than 4 mo, but if therapy was repeated every 2 mo patients experienced additive antitumor effects. Treatment activities of 50 kBq/kg were without toxicity but induced insufficient antitumor response in these high-tumor-burden patients. Remarkable antitumor activity by means of objective radiologic response or tumor marker decline was observed in 9 of 11 evaluable patients. For advanced-stage patients, a treatment activity of 100 kBq/kg of Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable trade-off between toxicity and biochemical response.
[Mh] Termos MeSH primário: Actínio/uso terapêutico
Partículas alfa/uso terapêutico
Dipeptídeos/uso terapêutico
Compostos Heterocíclicos com 1 Anel/uso terapêutico
Neoplasias de Próstata Resistentes à Castração/patologia
Neoplasias de Próstata Resistentes à Castração/radioterapia
[Mh] Termos MeSH secundário: Idoso
Seres Humanos
Masculino
Meia-Idade
Metástase Neoplásica
Radiometria
Dosagem Radioterapêutica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dipeptides); 0 (Heterocyclic Compounds, 1-Ring); 0 (PSMA-617); NIK1K0956U (Actinium)
[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:170415
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.117.191395


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[PMID]:27068756
[Au] Autor:Landsberger S; Tamalis D; Leblanc C; Yoho MD
[Ad] Endereço:University of Texas at Austin, Nuclear Engineering Teaching Laboratory, Pickle Research Campus, R-9000, Austin, TX 78712, USA; Enviroklean Product Development Inc. (EPDI), 9227 Thomasville Road, Houston, TX 77064, USA.
[Ti] Título:Disequilibrium in the uranium and actinium series in oil scale samples.
[So] Source:J Environ Radioact;166(Pt 1):126-129, 2017 Jan.
[Is] ISSN:1879-1700
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We have investigated the disequilibrium of the uranium and actinium series and have found both Ra (90,200 ± 4300 Bq/kg) and Ra have activity concentrations orders of magnitude higher that U (1.83 ± 0.36 Bq/kg) and Th (7.0 ± 0.4) which are at the head of the decay series. As well the activity concentration of Pb (24,400 ± 1200 Bg/kg) was about 3.6 times less than Ra. Once an efficiency curve was constructed summing corrections for specific isotopes in the decay change also needed to be taken in consideration. Furthermore, self-attenuation of the photons especially the 46.5 keV belonging to Pb was calculated to be 78% since the scale had elevated elemental concentrations of high-Z elements such as barium and strontium.
[Mh] Termos MeSH primário: Actínio/análise
Campos de Petróleo e Gás
Monitoramento de Radiação
Poluentes Radioativos do Solo/análise
Urânio/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Soil Pollutants, Radioactive); 4OC371KSTK (Uranium); NIK1K0956U (Actinium)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160413
[St] Status:MEDLINE


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[PMID]:27390158
[Au] Autor:Kratochwil C; Bruchertseifer F; Giesel FL; Weis M; Verburg FA; Mottaghy F; Kopka K; Apostolidis C; Haberkorn U; Morgenstern A
[Ad] Endereço:Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany clemens.kratochwil@med.uni-heidelberg.de.
[Ti] Título:225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.
[So] Source:J Nucl Med;57(12):1941-1944, 2016 Dec.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to Ac-PSMA-617 therapy. METHODS: Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with Ga-PSMA-11 PET/CT. RESULTS: Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect. CONCLUSION: Targeted α-therapy with Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.
[Mh] Termos MeSH primário: Actínio
Partículas alfa/uso terapêutico
Antígenos de Superfície/metabolismo
Dipeptídeos/uso terapêutico
Glutamato Carboxipeptidase II/metabolismo
Compostos Heterocíclicos com 1 Anel/uso terapêutico
Neoplasias de Próstata Resistentes à Castração/patologia
Neoplasias de Próstata Resistentes à Castração/radioterapia
Radioisótopos/uso terapêutico
[Mh] Termos MeSH secundário: Partículas beta/uso terapêutico
Seres Humanos
Lutécio/uso terapêutico
Masculino
Metástase Neoplásica
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem
Neoplasias de Próstata Resistentes à Castração/metabolismo
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Surface); 0 (Dipeptides); 0 (Heterocyclic Compounds, 1-Ring); 0 (PSMA-617); 0 (Radioisotopes); 5H0DOZ21UJ (Lutetium); EC 3.4.17.21 (Glutamate Carboxypeptidase II); EC 3.4.17.21 (glutamate carboxypeptidase II, human); NIK1K0956U (Actinium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160709
[St] Status:MEDLINE


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[PMID]:27127217
[Au] Autor:Behling K; Maguire WF; López Puebla JC; Sprinkle SR; Ruggiero A; O'Donoghue J; Gutin PH; Scheinberg DA; McDevitt MR
[Ad] Endereço:Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York behlingk@mskcc.org m-mcdevitt@ski.mskcc.org.
[Ti] Título:Vascular Targeted Radioimmunotherapy for the Treatment of Glioblastoma.
[So] Source:J Nucl Med;57(10):1576-1582, 2016 Oct.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glioblastoma is characterized by an aggressive and aberrant vascular network that promotes tumor progression and hinders effective treatment; the median survival is 16 mo despite standard-of-care therapies. There is a need to improve therapeutic options for this disease. We hypothesized that antibody targeting of the vascular endothelium of glioblastoma with cytotoxic short-range, high-energy α-particles would be an effective therapeutic approach. METHODS: E4G10, an antibody directed at an epitope of monomeric vascular endothelium cadherin that is expressed in tumor neovasculature and on endothelial progenitor cells in the bone marrow, was labeled with α-particle-emitting Ac. Pharmacokinetic studies investigated the tissue distribution and blood clearance of the Ac-E4G10 radioimmunoconstruct in a transgenic Nestin-tumor virus A (Ntva) mouse model of high-grade glioblastoma. Histologic analysis was used to demonstrate local therapeutic effects in treated brain tumor sections. Radioimmunotherapy with Ac-E4G10 was performed in Ntva mice to assess overall survival alone and in combination with temozolomide, the standard-of-care chemotherapeutic agent. RESULTS: Ac-E4G10 was found to accumulate in tissues expressing the target antigen. Antivascular α-particle therapy of glioblastoma in the transgenic Ntva model resulted in significantly improved survival compared with controls and potent control of tumor growth. Adding the chemotherapeutic temozolomide to the treatment increased survival to 30 d (vs. 9 d for vehicle-treated animals). Histologic analyses showed a remodeled glioblastoma vascular microenvironment. CONCLUSION: Targeted α-particle antivascular therapy is shown for the first time to be effective in increasing overall survival in a solid tumor in a clinically relevant transgenic glioblastoma mouse model.
[Mh] Termos MeSH primário: Vasos Sanguíneos/efeitos da radiação
Neoplasias Encefálicas/irrigação sanguínea
Neoplasias Encefálicas/radioterapia
Glioblastoma/irrigação sanguínea
Glioblastoma/radioterapia
Radioimunoterapia/métodos
[Mh] Termos MeSH secundário: Actínio
Partículas alfa/uso terapêutico
Animais
Anticorpos Monoclonais/química
Anticorpos Monoclonais/farmacocinética
Anticorpos Monoclonais/uso terapêutico
Vasos Sanguíneos/metabolismo
Neoplasias Encefálicas/metabolismo
Neoplasias Encefálicas/patologia
Linhagem Celular Tumoral
Glioblastoma/metabolismo
Glioblastoma/patologia
Seres Humanos
Camundongos
Gradação de Tumores
Radioquímica
Dosagem Radioterapêutica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); NIK1K0956U (Actinium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160430
[St] Status:MEDLINE


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[PMID]:26761207
[Au] Autor:Nafee SS; Shaheen SA; Al-Ramady AM
[Ad] Endereço:Physics Department, Faculty of Science, King Abdulaziz University, Jeddah, 20589, Saudi Arabia.
[Ti] Título:Nuclear Data Evaluation for Mass Chain A=217:Odd-Proton Nuclei.
[So] Source:PLoS One;11(1):e0146182, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thallium (81(217)Tl, Bismuth (83(217)Bi), Astatine (85(217)At), Francium (87(217)Fr), Actinium (89(217)Ac) and Protactinium (91(217)Pa) are of odd-proton numbers among the mass chain A = 217. In the present work, the half-lives and gamma transitions for the six nuclei have been studied and adopted based on the recently published interactions or unevaluated nuclear data sets XUNDL. The Q (α) has been updated based on the recent published work of the Atomic Mass Evaluation AME2012 as well. Moreover, the total conversion electrons as well as the K-Shell to L-Shell, L-Shell to M-Shell and L-Shell to N-Shell Conversion Electron Ratios have been calculated using BrIcc code v2.3. An updated skeleton decay scheme for each of the above nuclei has been presented here. The decay hindrance factors (HF) calculated using the ALPHAD program, which is available from Brookhaven National Laboratory's website, have been calculated for the α- decay data sets for (221)Fr-, (221)Ac- and (221)Pa-α-decays.
[Mh] Termos MeSH primário: Partículas alfa
Prótons
[Mh] Termos MeSH secundário: Actínio/química
Astato/química
Bismuto/química
Elétrons
Frâncio/química
Raios gama
Meia-Vida
Probabilidade
Protoactínio/química
Radioisótopos
Síncrotrons
Tálio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protons); 0 (Radioisotopes); 0S6855V29M (Protactinium); 15TEQ7D2QF (Francium); AD84R52XLF (Thallium); NIK1K0956U (Actinium); U015TT5I8H (Bismuth); XI595HAL7H (Astatine)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160114
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0146182


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[PMID]:26586724
[Au] Autor:Zhu C; Bandekar A; Sempkowski M; Banerjee SR; Pomper MG; Bruchertseifer F; Morgenstern A; Sofou S
[Ad] Endereço:Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ 08854.
[Ti] Título:Nanoconjugation of PSMA-Targeting Ligands Enhances Perinuclear Localization and Improves Efficacy of Delivered Alpha-Particle Emitters against Tumor Endothelial Analogues.
[So] Source:Mol Cancer Ther;15(1):106-113, 2016 Jan.
[Is] ISSN:1538-8514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aims to evaluate the effect on killing efficacy of the intracellular trafficking patterns of α-particle emitters by using different radionuclide carriers in the setting of targeted antivascular α-radiotherapy. Nanocarriers (lipid vesicles) targeted to the prostate-specific membrane antigen (PSMA), which is unique to human neovasculature for a variety of solid tumors, were loaded with the α-particle generator actinium-225 and were compared with a PSMA-targeted radiolabeled antibody. Actinium-225 emits a total of four α-particles per decay, providing highly lethal and localized irradiation of targeted cells with minimal exposure to surrounding healthy tissues. Lipid vesicles were derivatized with two types of PSMA-targeting ligands: a fully human PSMA antibody (mAb) and a urea-based, low-molecular-weight agent. Target selectivity and extent of internalization were evaluated on monolayers of human endothelial cells (HUVEC) induced to express PSMA in static incubation conditions and in a flow field. Both types of radiolabeled PSMA-targeted vesicles exhibit similar killing efficacy, which is greater than the efficacy of the radiolabeled control mAb when compared on the basis of delivered radioactivity per cell. Fluorescence confocal microscopy demonstrates that targeted vesicles localize closer to the nucleus, unlike antibodies which localize near the plasma membrane. In addition, targeted vesicles cause larger numbers of dsDNAs per nucleus of treated cells compared with the radiolabeled mAb. These findings demonstrate that radionuclide carriers, such as PSMA-targeted lipid-nanocarriers, which localize close to the nucleus, increase the probability of α-particle trajectories crossing the nuclei, and, therefore, enhance the killing efficacy of α-particle emitters.
[Mh] Termos MeSH primário: Partículas alfa
Antígenos de Superfície/metabolismo
Glutamato Carboxipeptidase II/antagonistas & inibidores
Glutamato Carboxipeptidase II/metabolismo
Ligantes
Nanoconjugados
Compostos Radiofarmacêuticos/administração & dosagem
[Mh] Termos MeSH secundário: Actínio
Transporte Biológico
Linhagem Celular
Sobrevivência Celular/efeitos dos fármacos
Células Endoteliais/metabolismo
Citometria de Fluxo
Histonas/metabolismo
Seres Humanos
Espaço Intracelular
Lipídeos
Masculino
Microscopia de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antigens, Surface); 0 (H2AFX protein, human); 0 (Histones); 0 (Ligands); 0 (Lipids); 0 (Nanoconjugates); 0 (Radiopharmaceuticals); EC 3.4.17.21 (Glutamate Carboxypeptidase II); EC 3.4.17.21 (glutamate carboxypeptidase II, human); NIK1K0956U (Actinium)
[Em] Mês de entrada:1610
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151121
[St] Status:MEDLINE
[do] DOI:10.1158/1535-7163.MCT-15-0207


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[PMID]:25998714
[Au] Autor:Larson SM; Carrasquillo JA; Cheung NK; Press OW
[Ad] Endereço:Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
[Ti] Título:Radioimmunotherapy of human tumours.
[So] Source:Nat Rev Cancer;15(6):347-60, 2015 Jun.
[Is] ISSN:1474-1768
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The eradication of cancer remains a vexing problem despite recent advances in our understanding of the molecular basis of neoplasia. One therapeutic approach that has demonstrated potential involves the selective targeting of radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Such radioimmunotherapy (RIT) permits the delivery of a high dose of therapeutic radiation to cancer cells, while minimizing the exposure of normal cells. Although this approach has been investigated for several decades, the cumulative advances in cancer biology, antibody engineering and radiochemistry in the past decade have markedly enhanced the ability of RIT to produce durable remissions of multiple cancer types.
[Mh] Termos MeSH primário: Neoplasias/radioterapia
Radioimunoterapia/métodos
[Mh] Termos MeSH secundário: Actínio/administração & dosagem
Actínio/uso terapêutico
Partículas alfa/uso terapêutico
Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/farmacologia
Ensaios Clínicos como Assunto
Neoplasias Hematológicas/radioterapia
Seres Humanos
Terapia de Alvo Molecular/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); NIK1K0956U (Actinium)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150523
[St] Status:MEDLINE
[do] DOI:10.1038/nrc3925


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[PMID]:25931476
[Au] Autor:Matson ML; Villa CH; Ananta JS; Law JJ; Scheinberg DA; Wilson LJ
[Ad] Endereço:Department of Chemistry, and the Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, Texas.
[Ti] Título:Encapsulation of α-Particle-Emitting 225Ac3+ Ions Within Carbon Nanotubes.
[So] Source:J Nucl Med;56(6):897-900, 2015 Jun.
[Is] ISSN:1535-5667
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:UNLABELLED: (225)Ac(3+) is a generator of α-particle-emitting radionuclides with 4 net α-particle decays that can be used therapeutically. Targeting (225)Ac(3+) by use of ligands conjugated to traditional bifunctional chelates limits the amount of (225)Ac(3+) that can be delivered. Ultrashort, single-walled carbon nanotubes (US-tubes), previously demonstrated as sequestering agents of trivalent lanthanide ions and small molecules, also successfully incorporate (225)Ac(3+). METHODS: Aqueous loading of both (225)Ac(3+) ions and Gd(3+) ions via bath sonication was used to construct (225)Ac@gadonanotubes ((225)Ac@GNTs). The (225)Ac@GNTs were subsequently challenged with heat, time, and human serum. RESULTS: US-tubes internally loaded with both (225)Ac(3+) ions and Gd(3+) ions show 2 distinct populations of (225)Ac(3+) ions: one rapidly lost in human serum and one that remains bound to the US-tubes despite additional challenge with heat, time, and serum. The presence of the latter population depended on cosequestration of Gd(3+) and (225)Ac(3+) ions. CONCLUSION: US-tubes successfully sequester (225)Ac(3+) ions in the presence of Gd(3+) ions and retain them after a human serum challenge, rendering (225)Ac@GNTs candidates for radioimmunotherapy for delivery of (225)Ac(3+) ions at higher concentrations than is currently possible for traditional ligand carriers.
[Mh] Termos MeSH primário: Actínio/química
Partículas alfa
Gadolínio/química
Íons
Nanotubos de Carbono/química
Radioimunoterapia/instrumentação
[Mh] Termos MeSH secundário: Quelantes/química
Meios de Contraste/química
Diagnóstico por Imagem
Seres Humanos
Ligantes
Nanotecnologia
Radioimunoterapia/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chelating Agents); 0 (Contrast Media); 0 (Ions); 0 (Ligands); 0 (Nanotubes, Carbon); AU0V1LM3JT (Gadolinium); NIK1K0956U (Actinium)
[Em] Mês de entrada:1508
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150502
[St] Status:MEDLINE
[do] DOI:10.2967/jnumed.115.158311


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[PMID]:25684650
[Au] Autor:Wilson JJ; Ferrier M; Radchenko V; Maassen JR; Engle JW; Batista ER; Martin RL; Nortier FM; Fassbender ME; John KD; Birnbaum ER
[Ad] Endereço:Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, NM, 87545, USA. Electronic address: jjwilson@lanl.gov.
[Ti] Título:Evaluation of nitrogen-rich macrocyclic ligands for the chelation of therapeutic bismuth radioisotopes.
[So] Source:Nucl Med Biol;42(5):428-38, 2015 May.
[Is] ISSN:1872-9614
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The use of α-emitting isotopes for radionuclide therapy is a promising treatment strategy for small micro-metastatic disease. The radioisotope (213)Bi is a nuclide that has found substantial use for targeted α-therapy (TAT). The relatively unexplored aqueous chemistry of Bi(3+), however, hinders the development of bifunctional chelating agents that can successfully deliver these Bi radioisotopes to the tumor cells. Here, a novel series of nitrogen-rich macrocyclic ligands is explored for their potential use as Bi-selective chelating agents. METHODS: The ligands, 1,4,7,10-tetrakis(pyridin-2-ylmethyl)-1,4,7,10-tetraazacyclododecane (L(py)), 1,4,7,10-tetrakis(3-pyridazylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyd)), 1,4,7,10-tetrakis(4-pyrimidylmethyl)-1,4,7,10-tetraazacyclododecane (L(pyr)), and 1,4,7,10-tetrakis(2-pyrazinylmethyl)-1,4,7,10-tetraazacyclododecane (L(pz)), were prepared by a previously reported method and investigated here for their abilities to bind Bi radioisotopes. The commercially available and commonly used ligands 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and N-[(R)-2-amino-3-(p-isothiocyanato-phenyl)propyl]-trans-(S,S)- cyclohexane-1,2-diamine-N,N,N',N",N"-pentaacetic acid (CHX-A''-DTPA) were also explored for comparative purposes. Radio-thin-layer chromatography (TLC) was used to measure the binding kinetics and stabilities of the complexes formed. The long-lived isotope, (207)Bi (t(1/2)=32 years), was used for these studies. Density functional theory (DFT) calculations were also employed to probe the ligand interactions with Bi(3+) and the generator parent ion Ac(3+). RESULTS: In contrast to DOTA and CHX-A''-DTPA, these nitrogen-rich macrocycles selectively chelate Bi(3+) in the presence of the parent isotope Ac(3+). Among the four tested, L(py) was found to exhibit optimal Bi(3+)-binding kinetics and complex stability. L(py) complexes Bi(3+) more rapidly than DOTA, yet the resulting complexes are of similar stability. DFT calculations corroborate the experimentally observed selectivity of these ligands for Bi(3+) over Ac(3+). CONCLUSION: Taken together, these data implicate L(py) as a valuable chelating agent for the delivery of (213)Bi. Its selectivity for Bi(3+) and rapid and stable labeling properties warrant further investigation and biological studies.
[Mh] Termos MeSH primário: Bismuto/química
Bismuto/uso terapêutico
Quelantes/química
Compostos Macrocíclicos/química
Nitrogênio/química
Radioisótopos
[Mh] Termos MeSH secundário: Actínio/química
Partículas alfa/uso terapêutico
Ligação Competitiva
Ácido Edético/química
Marcação por Isótopo
Cinética
Ligantes
Teoria Quântica
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chelating Agents); 0 (Ligands); 0 (Macrocyclic Compounds); 0 (Radioisotopes); 9G34HU7RV0 (Edetic Acid); N762921K75 (Nitrogen); NIK1K0956U (Actinium); U015TT5I8H (Bismuth)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150406
[Lr] Data última revisão:
150406
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150217
[St] Status:MEDLINE


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[PMID]:25596759
[Au] Autor:Radchenko V; Engle JW; Wilson JJ; Maassen JR; Nortier FM; Taylor WA; Birnbaum ER; Hudston LA; John KD; Fassbender ME
[Ad] Endereço:Los Alamos National Laboratory, P.O. Box 1663, Los Alamos, NM 87545, United States.
[Ti] Título:Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes.
[So] Source:J Chromatogr A;1380:55-63, 2015 Feb 06.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% ß(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 µCi).
[Mh] Termos MeSH primário: Actínio/isolamento & purificação
Prótons
Tório/isolamento & purificação
[Mh] Termos MeSH secundário: Cromatografia por Troca Iônica
Seres Humanos
Extração Líquido-Líquido
Tório/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Protons); 60YU5MIG9W (Thorium); NIK1K0956U (Actinium)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:150124
[Lr] Data última revisão:
150124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150119
[St] Status:MEDLINE



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