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1.
Data Brief ; 34: 106758, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33537375

RESUMO

The data provided in this article is related to the research article entitled "Phase stabilization and oxidation of a continuous composition spread multi-principal element (AlFeNiTiVZr)1-xCrx alloy" [1]. This data article describes the high-throughput synthesis and characterization processes of an (AlFeNiTiVZr)1-xCrx alloy system. Continuous composition spread (CCS) thin-film libraries were synthesized by co-depositing an AlFeNiTiVZr metal alloy target and Cr target via magnetron sputtering. Post-processing was performed on the sample libraries with a vacuum anneal at 873 K and an air anneal at 873 K. Compositional data was determined via WDS in order to verify parameters provided by an in-house sputter model. Crystallographic data was captured via synchrotron diffraction and diffractograms were compared as a function of the change in Cr concentration. These measurements were taken in order to observe phase behavior after oxidation throughout the composition library. Furthermore, vibrational spectrographic data is provided of the oxidized library to show surface speciation along the composition gradient of the alloy system. The structural and oxidative behavior of the (AlFeNiTiVZr)1-xCrx alloy can be analysed using the data provided in this article. Additionally, this characterization dataset can be utilized in machine learning algorithms for determining important features and parameters for future hypothesis generation of functional multi-principal element alloys (MPEAs).

2.
ACS Comb Sci ; 18(9): 596-603, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27494349

RESUMO

Multiprincipal element high entropy alloys stabilized as a single alloy phase represent a new material system with promising properties, such as high corrosion and creep resistance, sluggish diffusion, and high temperature tensile strength. However, the mechanism of stabilization to form single phase alloys is controversial. Early studies hypothesized that a large entropy of mixing was responsible for stabilizing the single phase; more recent work has proposed that the single-phase solid solution is the result of mutual solubility of the principal elements. Here, we demonstrate the first self-consistent study of the relative importance of these two proposed mechanisms. In situ high-throughput synchrotron diffraction studies were used to monitor the stability of the single phase alloy in thin-film (Al1-x-yCuxMoy)FeNiTiVZr composition spread samples. Our results indicate that a metastable solid solution can be captured via the rapid quenching typical of physical vapor deposition processes, but upon annealing the solid-solution phase stability is primarily governed by mutual miscibility.


Assuntos
Ligas/química , Técnicas de Química Combinatória , Corrosão , Entropia , Teste de Materiais , Estrutura Molecular , Solubilidade , Propriedades de Superfície , Temperatura
3.
Mol Cancer Ther ; 11(6): 1365-72, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22491799

RESUMO

Small-molecule ligands specific for tumor-associated surface receptors have wide applications in cancer diagnosis and therapy. Achieving high-affinity binding to the desired target is important for improving detection limits and for increasing therapeutic efficacy. However, the affinity required for maximal binding and retention remains unknown. Here, we present a systematic study of the effect of small-molecule affinity on tumor uptake in vivo with affinities spanning a range of three orders of magnitude. A pretargeted bispecific antibody with different binding affinities to different DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based small molecules is used as a receptor proxy. In this particular system targeting carcinoembryonic antigen, a small-molecule-binding affinity of 400 pmol/L was sufficient to achieve maximal tumor targeting, and an improvement in affinity to 10 pmol/L showed no significant improvement in tumor uptake at 24 hours postinjection. We derive a simple mathematical model of tumor targeting using measurable parameters that correlates well with experimental observations. We use relations derived from the model to develop design criteria for the future development of small-molecule agents for targeted cancer therapeutics.


Assuntos
Anticorpos Biespecíficos/metabolismo , Quelantes/farmacocinética , Complexos de Coordenação/farmacocinética , Compostos Heterocíclicos com 1 Anel/farmacocinética , Neoplasias Experimentais/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Animais , Anticorpos Biespecíficos/química , Antígeno Carcinoembrionário/metabolismo , Células Cultivadas , Haptenos , Humanos , Radioisótopos de Índio , Lutécio , Camundongos , Camundongos Nus , Modelos Biológicos , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Neoplasias Experimentais/radioterapia , Radioimunoterapia , Radioisótopos , Distribuição Tecidual , Transplante Heterólogo
4.
Nucl Med Biol ; 38(2): 223-33, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21315278

RESUMO

INTRODUCTION: In pretargeted radioimmunotherapy (PRIT), a bifunctional antibody is administered and allowed to pre-localize to tumor cells. Subsequently, a chelated radionuclide is administered and captured by cell-bound antibody while unbound hapten clears rapidly from the body. We aim to engineer high-affinity binders to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelates for use in PRIT applications. METHODS: We mathematically modeled antibody and hapten pharmacokinetics to analyze hapten tumor retention as a function of hapten binding affinity. Motivated by model predictions, we used directed evolution and yeast surface display to affinity mature the 2D12.5 antibody to DOTA, reformatted as a single chain variable fragment (scFv). RESULTS: Modeling predicts that for high antigen density and saturating bsAb dose, a hapten-binding affinity of 100 pM is needed for near-maximal hapten retention. We affinity matured 2D12.5 with an initial binding constant of about 10 nM to DOTA-yttrium chelates. Affinity maturation resulted in a 1000-fold affinity improvement to biotinylated DOTA-yttrium, yielding an 8.2±1.9 picomolar binder. The high-affinity scFv binds DOTA complexes of lutetium and gadolinium with similar picomolar affinity and indium chelates with low nanomolar affinity. When engineered into a bispecific antibody construct targeting carcinoembryonic antigen, pretargeted high-affinity scFv results in significantly higher tumor retention of a (111)In-DOTA hapten compared to pretargeted wild-type scFv in a xenograft mouse model. CONCLUSIONS: We have engineered a versatile, high-affinity, DOTA-chelate-binding scFv. We anticipate it will prove useful in developing pretargeted imaging and therapy protocols to exploit the potential of a variety of radiometals.


Assuntos
Anticorpos/genética , Afinidade de Anticorpos , Compostos Heterocíclicos com 1 Anel/química , Imagem Molecular/métodos , Engenharia de Proteínas/métodos , Radioimunoterapia/métodos , Radioisótopos/uso terapêutico , Sequência de Aminoácidos , Animais , Anticorpos/química , Anticorpos/imunologia , Anticorpos/metabolismo , Linhagem Celular Tumoral , Quelantes/química , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/radioterapia , Haptenos/imunologia , Humanos , Cinética , Masculino , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Radioisótopos/química , Anticorpos de Cadeia Única/química , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia , Anticorpos de Cadeia Única/metabolismo
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