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https://www.readbyqxmd.com/read/29160082/cyclic-versus-noncyclic-chelating-scaffold-for-89zr-labeled-zegfr-2377-affibody-bioconjugates-targeting-epidermal-growth-factor-receptor-overexpression
#1
Dominik Summer, Javad Garousi, Maryam Oroujeni, Bogdan Mitran, Ken G Andersson, Anzhelika Vorobyeva, John Löfblom, Anna Orlova, Vladimir Tolmachev, Clemens Decristoforo
Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure...
November 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29125701/data-driven-reduced-order-model-of-microtubule-mechanics
#2
Yan Feng, Sorin Mitran
A beam element is constructed for microtubules based upon data reduction of the results from atomistic simulation of the carbon backbone chain of αβ-tubulin dimers. The data base of mechanical responses to various types of loads from atomistic simulation is reduced to dominant modes. The dominant modes are subsequently used to construct the stiffness matrix of a beam element that captures the anisotropic behavior and deformation mode coupling that arises from a microtubule's spiral structure. In contrast to standard Euler-Bernoulli or Timoshenko beam elements, the link between forces and node displacements results not from hypothesized deformation behavior, but directly from the data obtained by molecular scale simulation...
November 10, 2017: Cytoskeleton
https://www.readbyqxmd.com/read/29116215/comparative-evaluation-of-tumor-targeting-using-the-anti-her2-adapt-scaffold-protein-labeled-at-the-c-terminus-with-indium-111-or-technetium-99m
#3
Javad Garousi, Sarah Lindbo, Bogdan Mitran, Jos Buijs, Anzhelika Vorobyeva, Anna Orlova, Vladimir Tolmachev, Sophia Hober
ABD-Derived Affinity Proteins (ADAPTs) is a novel class of engineered scaffold proteins derived from an albumin-binding domain of protein G. The use of ADAPT6 derivatives as targeting moiety have provided excellent preclinical radionuclide imaging of human epidermal growth factor 2 (HER2) tumor xenografts. Previous studies have demonstrated that selection of nuclide and chelator for its conjugation has an appreciable effect on imaging properties of scaffold proteins. In this study we performed a comparative evaluation of the anti-HER2 ADAPT having an aspartate-glutamate-alanine-valine-aspartate-alanine-asparagine-serine (DEAVDANS) N-terminal sequence and labeled at C-terminus with (99m)Tc using a cysteine-containing peptide based chelator, glycine-serine-serine-cysteine (GSSC), and a similar variant labeled with (111)In using a maleimido derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator...
November 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29097932/high-contrast-pet-imaging-of-grpr-expression-in-prostate-cancer-using-cobalt-labeled-bombesin-antagonist-rm26
#4
Bogdan Mitran, Helge Thisgaard, Ulrika Rosenström, Johan Hygum Dam, Mats Larhed, Vladimir Tolmachev, Anna Orlova
High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a (55)Co-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with (57)Co and (55)Co, stability, binding specificity, and in vitro and in vivo characteristics of (57)Co-NOTA-PEG2-RM26 were studied. NOTA-PEG2-RM26 was successfully radiolabeled with (57)Co and (55)Co with high yields and demonstrated high stability...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29039474/evaluation-of-a-radiocobalt-labelled-affibody-molecule-for-imaging-of-human-epidermal-growth-factor-receptor-3-expression
#5
Maria Rosestedt, Ken G Andersson, Bogdan Mitran, Sara S Rinne, Vladimir Tolmachev, John Löfblom, Anna Orlova, Stefan Ståhl
The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated...
October 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28864631/radionuclide-tumor-targeting-using-adapt-scaffold-proteins-aspects-of-label-positioning-and-residualizing-properties-of-the-label
#6
Sarah Lindbo, Javad Garousi, Bogdan Mitran, Mohamed Altai, Jos Buijs, Anna Orlova, Sophia Hober, Vladimir Tolmachev
Visualization of cancer-associated alterations of molecular phenotype using radionuclide imaging is a non-invasive approach to stratify patients for targeted therapies. The engineered scaffold protein ABD-.derived affinity protein (ADAPT) is a promising tracer for radionuclide molecular imaging due to its small size (6.5 kDa), that provides precondition for efficient tumor penetration and rapid clearance. Previous studies demonstrated that the human epidermal growth factor receptor type 2 (HER2)-targeting ADAPT6 labeled with radiometals at the N-terminus provides imaging of HER2 expression in xenografts a few hours after injection...
September 1, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28810153/evaluation-of-affibody-molecule-based-pna-mediated-radionuclide-pretargeting-development-of-an-optimized-conjugation-protocol-and-177-lu-labeling
#7
Mohamed Altai, Kristina Westerlund, Justin Velletta, Bogdan Mitran, Hadis Honarvar, Amelie Eriksson Karlström
INTRODUCTION: We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide (177)Lu. We also studied the biodistribution profile of (177)Lu-HP2 in mice, and evaluated pretargeting with (177)Lu-HP2 in vitro and in vivo. METHODS: The biodistribution profile of (177)Lu-HP2 was evaluated in NMRI mice and compared to the previously studied (111)In-HP2...
July 12, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28729680/the-use-of-radiocobalt-as-a-label-improves-imaging-of-egfr-using-dota-conjugated-affibody-molecule
#8
Javad Garousi, Ken G Andersson, Johan H Dam, Birgitte B Olsen, Bogdan Mitran, Anna Orlova, Jos Buijs, Stefan Ståhl, John Löfblom, Helge Thisgaard, Vladimir Tolmachev
Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28440350/high-frequency-ultrasonography-of-the-hand-versus-anti-ra33-evaluation-in-early-rheumatoid-arthritis-a-pilot-study
#9
Andreea Lili Barbulescu, Paulina Lucia Ciurea, Carmen Mitran, Beatrice Andreea Chisalau, Cristina Dorina Parvanescu, Sineta Cristina Firulescu, Maria Balasoiu, Mihail Virgil Boldeanu, Horatiu Popoviciu, Florentin Ananu Vreju
AIM: Accurate diagnosis and early treatment in rheumatoid arthritis (RA) can lead to a good outcome and a correct management of the disease. We aimed toinvestigate the prognostic value of anti-RA33 antibodies, by evaluating the relationship with ultrasonographic (US) findings in patients with early RA. MATERIAL AND METHODS: We performed a prospective study which included 29 patients, diagnosed with early RA according to the ACR/EULAR 2010 criteria and 21 sex and age-matched control subjects...
April 22, 2017: Medical Ultrasonography
https://www.readbyqxmd.com/read/28422565/ascorbic-acid-deficiency-in-patients-with-lichen-planus
#10
Ilinca Nicolae, Cristina Iulia Mitran, Madalina Irina Mitran, Corina Daniela Ene, Mircea Tampa, Simona Roxana Georgescu
OBJECTIVES: Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin. MATERIAL AND METHOD: We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects...
2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#11
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032026/synthesis-of-11-c-labeled-sulfonyl-carbamates-through-a-multicomponent-reaction-employing-sulfonyl-azides-alcohols-and-11-c-co
#12
Marc Y Stevens, Shiao Y Chow, Sergio Estrada, Jonas Eriksson, Veronika Asplund, Anna Orlova, Bogdan Mitran, Gunnar Antoni, Mats Larhed, Ola Åberg, Luke R Odell
We describe the development of a new methodology focusing on (11)C-labeling of sulfonyl carbamates in a multicomponent reaction comprised of a sulfonyl azide, an alkyl alcohol, and [(11)C]CO. A number of (11)C-labeled sulfonyl carbamates were synthesized and isolated, and the developed methodology was then applied in the preparation of a biologically active molecule. The target compound was obtained in 24±10 % isolated radiochemical yield and was evaluated for binding properties in a tumor cell assay; in vivo biodistribution and imaging studies were also performed...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/27933199/efficacy-and-tolerability-of-repository-corticotropin-injection-in-patients-with-persistently-active-sle-results-of-a-phase-4-randomised-controlled-pilot-study
#13
Richard Furie, Margaret Mitrane, Enxu Zhao, Maya Das, Daner Li, Patrice M Becker
OBJECTIVE: To evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic SLE. METHODS: This prospective, randomised, double-blind, phase 4, pilot study (NCT01753401) enrolled 38 patients with persistently active SLE involving skin and/or joints. Enrolled patients received RCI, 40 U daily or 80 U every other day, or volume-matched placebo gel, for 8 weeks, with dose tapering to twice weekly during weeks 5-8...
2016: Lupus Science & Medicine
https://www.readbyqxmd.com/read/27748899/feasibility-of-imaging-of-epidermal-growth-factor-receptor-expression-with-zegfr-2377-affibody-molecule-labeled-with-99mtc-using-a-peptide-based-cysteine-containing-chelator
#14
Ken G Andersson, Maryam Oroujeni, Javad Garousi, Bogdan Mitran, Stefan Ståhl, Anna Orlova, John Löfblom, Vladimir Tolmachev
The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets...
December 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27746580/swept-source-anatomic-optical-coherence-elastography-of-porcine-trachea
#15
Ruofei Bu, Hillel Price, Sorin Mitran, Carlton Zdanski, Amy L Oldenburg
Quantitative endoscopic imaging is at the vanguard of novel techniques in the assessment upper airway obstruction. Anatomic optical coherence tomography (aOCT) has the potential to provide the geometry of the airway lumen with high-resolution and in 4 dimensions. By coupling aOCT with measurements of pressure, optical coherence elastography (OCE) can be performed to characterize airway wall stiffness. This can aid in identifying regions of dynamic collapse as well as informing computational fluid dynamics modeling to aid in surgical decision-making...
2016: Proceedings of SPIE
https://www.readbyqxmd.com/read/27740752/influence-of-the-n-terminal-composition-on-targeting-properties-of-radiometal-labeled-anti-her2-scaffold-protein-adapt6
#16
Javad Garousi, Sarah Lindbo, Hadis Honarvar, Justin Velletta, Bogdan Mitran, Mohamed Altai, Anna Orlova, Vladimir Tolmachev, Sophia Hober
Radionuclide-imaging-based stratification of patients to targeted therapies makes cancer treatment more personalized and therefore more efficient. Albumin-binding domain derived affinity proteins (ADAPTs) constitute a novel group of imaging probes based on the scaffold of an albumin-binding domain (ABD). To evaluate how different compositions of the N-terminal sequence of ADAPTs influence their biodistribution, a series of human epidermal growth factor receptor type 2 (HER2)-binding ADAPT6 derivatives with different N-terminal sequences were created: GCH6DANS (2), GC(HE)3DANS (3), GCDEAVDANS (4), and GCVDANS(5)...
November 16, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27529191/comparative-evaluation-of-affibody-molecules-for-radionuclide-imaging-of-in-vivo-expression-of-carbonic-anhydrase-ix
#17
Javad Garousi, Hadis Honarvar, Ken G Andersson, Bogdan Mitran, Anna Orlova, Jos Buijs, John Löfblom, Fredrik Y Frejd, Vladimir Tolmachev
Overexpression of the enzyme carbonic anhydrase IX (CAIX) is documented for chronically hypoxic malignant tumors as well as for normoxic renal cell carcinoma. Radionuclide molecular imaging of CAIX would be useful for detection of hypoxic areas in malignant tumors, for patients' stratification for CAIX-targeted therapies, and for discrimination of primary malignant and benign renal tumors. Earlier, we have reported feasibility of in vivo radionuclide based imaging of CAIX expressing tumors using Affibody molecules, small affinity proteins based on a nonimmunoglobulin scaffold...
November 7, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27515177/effects-of-stone-size-on-the-comminution-process-and-efficiency-in-shock-wave-lithotripsy
#18
Ying Zhang, Isaac Nault, Sorin Mitran, Edwin S Iversen, Pei Zhong
The effects of stone size on the process and comminution efficiency of shock wave lithotripsy (SWL) were investigated in experiments, numerical simulations and scale analysis. Cylindrical BegoStone phantoms with approximately equal height and diameter of either 4, 7 or 10 mm, in a total aggregated mass of about 1.5 g, were treated in an electromagnetic shock wave lithotripter field. The resultant stone comminution was found to correlate closely with the average peak pressure, P+(avg), incident on the stones...
November 2016: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/27046595/the-virtual-pediatric-airways-workbench
#19
Cory W Quammen, Russell M Taylor, Pavel Krajcevski, Sorin Mitran, Andinet Enquobahrie, Richard Superfine, Brad Davis, Stephanie Davis, Carlton Zdanski
The Virtual Pediatric Airways Workbench (VPAW) is a patient-centered surgical planning software system targeted to pediatric patients with airway obstruction. VPAW provides an intuitive surgical planning interface for clinicians and supports quantitative analysis regarding prospective surgeries to aid clinicians deciding on potential surgical intervention. VPAW enables a full surgical planning pipeline, including importing DICOM images, segmenting the airway, interactive 3D editing of airway geometries to express potential surgical treatment planning options, and creating input files for offline geometric analysis and computational fluid dynamics simulations for evaluation of surgical outcomes...
2016: Studies in Health Technology and Informatics
https://www.readbyqxmd.com/read/27010700/increasing-the-net-negative-charge-by-replacement-of-dota-chelator-with-dotaga-improves-the-biodistribution-of-radiolabeled-second-generation-synthetic-affibody-molecules
#20
Kristina Westerlund, Hadis Honarvar, Emily Norrström, Joanna Strand, Bogdan Mitran, Anna Orlova, Amelie Eriksson Karlström, Vladimir Tolmachev
A promising strategy to enable patient stratification for targeted therapies is to monitor the target expression in a tumor by radionuclide molecular imaging. Affibody molecules (7 kDa) are nonimmunoglobulin scaffold proteins with a 25-fold smaller size than intact antibodies. They have shown an apparent potential as molecular imaging probes both in preclinical and clinical studies. Earlier, we found that hepatic uptake can be reduced by the incorporation of negatively charged purification tags at the N-terminus of Affibody molecules...
May 2, 2016: Molecular Pharmaceutics
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