Theranostic Intratumoral Convection-Enhanced Delivery of I-Omburtamab in Patients with Diffuse Intrinsic Pontine Glioma: Pharmacokinetics and Lesion Dosimetry.

Diffuse intrinsic pontine glioma (DIPG) is a rare childhood malignancy with poor prognosis. There are no effective treatment options other than external beam therapy. We conducted a pilot, first-in-human study using I-omburtamab imaging and theranostics as a therapeutic approach using a localized convection-enhanced delivery (CED) technique for administering radiolabeled antibody.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with I-omburtamab for leptomeningeal disease.

Background: Radiolabeled antibody I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance.

Feasibility of safe outpatient treatment in pediatric patients following intraventricular radioimmunotherapy with 131I-omburtamab for leptomeningeal disease.

Background: Radiolabeled antibody I-omburtamab was administered intraventricularly in patients with leptomeningeal disease under an institutionally approved study (#NCT03275402). Radiation safety precautions were tailored for individual patients, enabling outpatient treatment based on in-depth, evidence-based recommendations for such precautions. The imperative advancement of streamlined therapeutic administration procedures, eliminating the necessity for inpatient isolation and resource-intensive measures, holds pivotal significance.

Quantitative Cytochrome P450 3A4 Induction Risk Assessment Using Human Hepatocytes Complemented with Pregnane X Receptor-Activating Profiles.

Reliable in vitro to in vivo translation of cytochrome P450 (CYP) 3A4 induction potential is essential to support risk mitigation for compounds during pharmaceutical discovery and development. In this study, a linear correlation of CYP3A4 mRNA induction potential in human hepatocytes with the respective pregnane-X receptor (PXR) activation in a reporter gene assay using DPX2 cells was successfully demonstrated for 13 clinically used drugs. Based on this correlation, using rifampicin as a positive control, the magnitude of CYP3A4 mRNA induction for 71 internal compounds at several concentrations up to 10 M ( = 90) was predicted within 2-fold error for 64% of cases with only a few false positives (19%).

Phase 1 study of intraventricular I-omburtamab targeting B7H3 (CD276)-expressing CNS malignancies.

Background: The prognosis for metastatic and recurrent tumors of the central nervous system (CNS) remains dismal, and the need for newer therapeutic targets and modalities is critical. The cell surface glycoprotein B7H3 is expressed on a range of solid tumors with a restricted expression on normal tissues. We hypothesized that compartmental radioimmunotherapy (cRIT) with the anti-B7H3 murine monoclonal antibody omburtamab injected intraventricularly could safely target CNS malignancies.

On the Surface Modification of LLZTO with LiF via a Gas-Phase Approach and the Characterization of the Interfaces of LiF with LLZTO as Well as PEO+LiTFSI.

In this study we present gas-phase fluorination as a method to create a thin LiF layer on LiLaZrTaO (LLZTO). We compared these fluorinated films with LiF films produced by RF-magnetron sputtering, where we investigated the interface between the LLZTO and the deposited LiF showing no formation of a reaction layer. Furthermore, we investigated the ability of this LiF layer as a protection layer against LiCO formation in ambient air.

Quantifying intraventricular drug delivery utilizing programmable ventriculoperitoneal shunts as the intraventricular access device.

Purpose: Programmable ventriculoperitoneal shunts (pVP shunts) are increasingly utilized for intraventricular chemotherapy, radioimmunotherapy, and/or cellular therapy. Shunt adjustments allow optimization of drug concentrations in the thecal space with minimization in the peritoneum. This report assesses the success of the pVP shunt as an access device for intraventricular therapies.

Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients.

Background: Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests.

Methods: We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families.

Compositional Dependence of Li-Ion Conductivity in Garnet-Rich Composite Electrolytes for All-Solid-State Lithium-Ion Batteries-Toward Understanding the Drawbacks of Ceramic-Rich Composites.

Composite electrolytes comprising a polymer plus Li salt matrix and embedded fillers have the potential of realizing high lithium-ion conductivity, good mechanical properties, wide electrochemical operational window, and stability against metallic lithium, all of which are essential for the development of high-energy-density all-solid-state lithium-ion batteries. In this study, a solvent-free approach has been used to prepare composite electrolytes with tetragonal and cubic phase garnets synthesized nebulized spray pyrolysis with polyethylene oxide (PEO) being the polymer component. Electrochemical impedance spectroscopy (EIS) is used to examine a series of composites with different garnets and weight fractions.

Structural, Magnetic and Catalytic Properties of a New Vacancy Ordered Perovskite Type Barium Cobaltate BaCoO.

A new vacancy ordered, anion deficient perovskite modification with composition of BaCoO (Ba Co O □ ) has been prepared via a two-step heating process. Combined Rietveld analysis of neutron and X-ray powder diffraction data shows a novel ordering of oxygen vacancies not known before for barium cobaltates. A combination of neutron powder diffraction, magnetic measurements, and density functional theory (DFT) studies confirms G-type antiferromagnetic ordering.

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy.

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e.

Mast cell proliferation in the cerebrospinal fluid after intraventricular administration of anti-B7H3 immunotherapy.

Omburtamab is a B7H3-specific murine monoclonal antibody. B7H3 (CD 276) is a member of the B7 family of immune checkpoint co-inhibitory receptors overexpressed on many human malignancies. Radioimmunotherapy with I- or I-omburtamab administered in the cerebrospinal fluid (CSF), intraperitoneal or intratumoral cavity is currently under investigation for the treatment of CNS malignancies.

A commercial treatment planning system with a hybrid dose calculation algorithm for synchrotron radiotherapy trials.

Synchrotron Radiotherapy (SyncRT) is a preclinical radiation treatment which delivers synchrotron x-rays to cancer targets. SyncRT allows for novel treatments such as Microbeam Radiotherapy, which has been shown to have exceptional healthy tissue sparing capabilities while maintaining good tumour control. Veterinary trials in SyncRT are anticipated to take place in the near future at the Australian Synchrotron's Imaging and Medical Beamline (IMBL).

Prone positioning and convalescent plasma therapy in a critically ill pregnant woman with COVID-19.

Prone positioning is feasible in pregnancy and may have contributed to the positive outcome in this case. Doctors should not be reluctant to move a patient to a prone position just because they are pregnant.

Single nucleotide polymorphisms from candidate genes associated with nematode resistance and resilience in Corriedale and Pampinta sheep in Argentina.

Selective breeding of genetically resistant animals is considered a promising strategy to face the problem of nematode resistance to anthelmintics and mitigate concerns about the presence of chemical residues in animal food products and the environment. Gastrointestinal nematode resistance is a complex, multifactorial trait related to host immunity. However, the mechanisms underlying host resistance and response to infection remain to be fully elucidated.

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.

Entrectinib, a TRK/ROS1 inhibitor with anti-CNS tumor activity: differentiation from other inhibitors in its class due to weak interaction with P-glycoprotein.

Background: Studies evaluating the CNS penetration of a novel tyrosine kinase inhibitor, entrectinib, proved challenging, particularly due to discrepancies across earlier experiments regarding P-glycoprotein (P-gp) interaction and brain distribution. To address this question, we used a novel "apical efflux ratio" (AP-ER) model to assess P-gp interaction with entrectinib, crizotinib, and larotrectinib, and compared their brain-penetration properties.

Methods: AP-ER was designed to calculate P-gp interaction with the 3 drugs in vitro using P-gp-overexpressing cells.

Assessing Cerebrospinal Fluid Flow Dynamics in Pediatric Patients with Central Nervous System Tumors Treated with Intraventricular Radioimmunotherapy.

The incidence of abnormal cerebrospinal fluid (CSF) flow dynamics in children with central nervous system (CNS) tumors before intraventricular therapy has not been described. We performed a single-institution, retrospective review of patients with primary or metastatic CNS tumors treated between 2003 and 2018 (15 y). Patients underwent In-diethylenetriaminepentaacetic acid injection into the CSF intraventricular space followed by nuclear medicine imaging at 90 min, 4 h, 24 h, and 48 h (if required).

Deformational changes after convection-enhanced delivery in the pediatric brainstem.

Objective: In the brainstem, there are concerns regarding volumetric alterations following convection-enhanced delivery (CED). The relationship between distribution volume and infusion volume is predictably greater than one. Whether this translates into deformational changes and influences clinical management is unknown.

Technical advances in x-ray microbeam radiation therapy.

In the last 25 years microbeam radiation therapy (MRT) has emerged as a promising alternative to conventional radiation therapy at large, third generation synchrotrons. In MRT, a multi-slit collimator modulates a kilovoltage x-ray beam on a micrometer scale, creating peak dose areas with unconventionally high doses of several hundred Grays separated by low dose valley regions, where the dose remains well below the tissue tolerance level. Pre-clinical evidence demonstrates that such beam geometries lead to substantially reduced damage to normal tissue at equal tumour control rates and hence drastically increase the therapeutic window.

First experimental measurement of the effect of cardio-synchronous brain motion on the dose distribution during microbeam radiation therapy.

Purpose: Microbeam radiation therapy (MRT) is an emerging radiation oncology modality ideal for treating inoperable brain tumors. MRT employs quasi-parallel beams of low-energy x rays produced from modern synchrotrons. A tungsten carbide multislit collimator (MSC) spatially fractionates the broad beam into rectangular beams.

Film dosimetry studies for patient specific quality assurance in microbeam radiation therapy.

Microbeam radiation therapy (MRT) uses synchrotron arrays of X-ray microbeams to take advantage of the spatial fractionation effect for normal tissue sparing. In this study, radiochromic film dosimetry was performed for a treatment where MRT is introduced as a dose boost in a hypofractionated stereotactic radiotherapy (SRT) scheme. The isocenter dose was measured using an ionization chamber and two dimensional dose distributions were determined using radiochromic films.

Synchrotron Microbeam Radiation Therapy as a New Approach for the Treatment of Radioresistant Melanoma: Potential Underlying Mechanisms.

Purpose: Synchrotron microbeam radiation therapy (MRT) is a method that spatially distributes the x-ray beam into several microbeams of very high dose (peak dose), regularly separated by low-dose intervals (valley dose). MRT selectively spares normal tissues, relative to conventional (uniform broad beam [BB]) radiation therapy.

Methods And Materials: To evaluate the effect of MRT on radioresistant melanoma, B16-F10 murine melanomas were implanted into mice ears.