Comparative Preclinical Evaluation of HER2-Targeting ABD-Fused Affibody Molecules Lu-ABY-271 and Lu-ABY-027: Impact of DOTA Position on ABD Domain.

Radiolabeled Affibody-based targeting agent Lu-ABY-027, a fusion of an anti-HER2 Affibody molecule with albumin binding domain (ABD) site-specifically labeled at the C-terminus, has demonstrated a promising biodistribution profile in mice; binding of the construct to albumin prevents glomerular filtration and significantly reduces renal uptake. In this study, we tested the hypothesis that site-specific positioning of the chelator at helix 1 of ABD, at a maximum distance from the albumin binding site, would further increase the strength of binding to albumin and decrease the renal uptake. The new construct, ABY-271 with DOTA conjugated at the back of ABD, has been labelled with Lu.

Preclinical Evaluation of Tc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake.

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [Tc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface.

Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model.

Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis.

Computed tomography and clinical outcome in patients with severe traumatic brain injury.

Objective: To study: (i) acute computed tomography (CT) characteristics and clinical outcome; (ii) clinical course and (iii) Corticosteroid Randomisation after Significant Head Injury acute calculator protocol (CRASH) model and clinical outcome in patients with severe traumatic brain injury (sTBI).

Methods: Initial CT (CT) and CT 24 hours post-trauma (CT) were evaluated according to Marshall and Rotterdam classifications. Rancho Los Amigos Cognitive Scale-Revised (RLAS-R) and Glasgow Outcome Scale Extended (GOSE) were assessed at three months and one year post-trauma.

Successful treatment of a ruptured aneurysm at the vertebral artery-posterior inferior cerebellar artery junction and simultaneous treatment of the stenotic vertebral artery with a single flow-diverting stent: a case report.

Introduction: This is the first report on the simultaneous successful treatment of a large ruptured saccular aneurysm and stenotic parent artery with a single flow-diverting stent.

Case Presentation: We report the case of a 68-year-old Caucasian man with occlusion of the right vertebral artery and a ruptured aneurysm at the junction of the left posterior inferior cerebellar artery-left vertebral artery that was successfully treated by the deployment of a single flow-diverting stent in the stenotic left vertebral artery. Stent deployment was complicated by thrombotic occlusion of the basilar artery, which was successfully reopened.

Imaging of platelet-derived growth factor receptor β expression in glioblastoma xenografts using affibody molecule 111In-DOTA-Z09591.

Unlabelled: The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein.

Long-term follow-up of intracranial aneurysms treated with endovascular coiling: experience from one institution.

Background: Our aim was to evaluate the long-term treatment results in patients with intracranial aneurysms treated with endovascular techniques.

Methods: Forty-four patients treated due to intracranial aneurysms between 1996 and 2002 were investigated with a time-of-flight sequence magnetic resonance angiography (TOF MRA).

Results: Depending on the assessment, 47% to 51% of the treated aneurysms had a residual neck at the last digital subtraction angiography follow-up.

Design of an optimized scaffold for affibody molecules.

Affibody molecules are non-immunoglobulin-derived affinity proteins based on a three-helical bundle protein domain. Here, we describe the design process of an optimized Affibody molecule scaffold with improved properties and a surface distinctly different from that of the parental scaffold. The improvement was achieved by applying an iterative process of amino acid substitutions in the context of the human epidermal growth factor receptor 2 (HER2)-specific Affibody molecule Z(HER2:342).

Coil embolization of anterior circulation aneurysms supported by the Solitaire AB Neurovascular Remodeling Device.

Introduction: The purpose of the study is to evaluate patients with wide-necked or complex aneurysms of the anterior circulation who underwent Solitaire AB Neurovascular Remodeling Device-assisted coil embolization.

Methods: From February 2008 to March 2009, consecutive data were collected from 45 patients with anterior circulation aneurysms. Eighteen of the patients presented with acute subarachnoid hemorrhage.

Spontaneous resorption of intradural lumbar disc fragments.

Background Context: Intradural disc herniation is relatively rare complication of the spinal degenerative process that occurs most frequently in the lumbar part of the spine. Both myelographic and magnetic resonance features of this entity have been described, and the mechanism of intradural herniation has already been proposed and generally accepted. In this article, we present a case of spontaneous resorption of an intradural, fragmented intervertebral disc.

Affibody-mediated transferrin depletion for proteomics applications.

An Affibody (Affibody) ligand with specific binding to human transferrin was selected by phage display technology from a combinatorial protein library based on the staphylococcal protein A (SpA)-derived Z domain. Strong and selective binding of the selected Affibody ligand to transferrin was demonstrated using biosensor technology and dot blot analysis. Impressive specificity was demonstrated as transferrin was the only protein recovered by affinity chromatography from human plasma.

Hypofractionated conformal stereotactic radiotherapy for arteriovenous malformations.

Objective: Arteriovenous malformations (AVMs) are congenital vascular lesions that are associated with high morbidity and mortality if left untreated. There are several options for treatment, including radiotherapy. Safe and effective single-fraction radiotherapy for patients with large AVMs has been considered difficult.

Genetic design for facilitated production and recovery of recombinant proteins in Escherichia coli.

Genetic strategies have been used for more than two decades to improve bacterial bioprocesses and to simplify recovery procedures. Such strategies include the design of efficient expression vectors and the improvement of bacterial production strains in different ways, e.g.

Structure, specificity, and mode of interaction for bacterial albumin-binding modules.

We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin.