Synthesis and preclinical evaluation of [F]AlF-NODA-MP-C6-CTHRSSVVC as a PET tracer for CD163-positive tumor-infiltrating macrophages.

Positron emission tomography (PET) can provide information about tumor-associated macrophage (TAM) infiltration, as long as a suitable tracer is available. This study aimed to evaluate the radiolabeled peptide [F]AlF-NODA-MP-C6-CTHRSSVVC as a potential PET tracer for imaging of the CD163 receptor, which is expressed on M2-type tumor-associated macrophages. The conjugated peptide NODA-MP-C6-CTHRSSVVC was labeled with aluminum [F]fluoride.

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.

Effects of the adenosine A receptor antagonist KW6002 on the dopaminergic system, motor performance, and neuroinflammation in a rat model of Parkinson's disease.

Adenosine A-receptors (AR) and dopamine D-receptors (DR) are known to work together in a synergistic manner. Inhibiting ARs by genetic or pharmacological means can relief symptoms and have neuroprotective effects in certain conditions. We applied PET imaging to evaluate the impact of the AR antagonist KW6002 on DR availability and neuroinflammation in an animal model of Parkinson's disease.

Prenatal infection and adolescent social adversity affect microglia, synaptic density, and behavior in male rats.

Maternal infection during pregnancy and childhood social trauma have been associated with neurodevelopmental and affective disorders, such as schizophrenia, autism spectrum disorders, bipolar disorder and depression. These disorders are characterized by changes in microglial cells, which play a notable role in synaptic pruning, and synaptic deficits. Here, we investigated the effect of prenatal infection and social adversity during adolescence - either alone or in combination - on behavior, microglia, and synaptic density.

Serum Cystatin C Levels as a Predictor of Severity and Mortality Among Patients With COVID-19 Infection.

Introduction: The pandemic caused by SARS Corona Virus-2 (COVID-19) has caused widespread mortality globally. The hallmark of the disease is the "cytokine storm," which is caused due to dysregulated immune system activation. Numerous inflammatory markers are used to predict the severity and mortality of the infection.

Maternal infection during pregnancy aggravates the behavioral response to an immune challenge during adolescence in female rats.

Prenatal and early postnatal infection have been associated with changes in microglial activity and the development of psychiatric disorders. Here, we investigated the effect of prenatal immune activation and postnatal immune challenge, alone and combined, on behavior and microglial cell density in female Wistar rats. Pregnant rats were injected with poly I:C to induce a maternal immune activation (MIA).

Relating enhancer genetic variation across mammals to complex phenotypes using machine learning.

Protein-coding differences between species often fail to explain phenotypic diversity, suggesting the involvement of genomic elements that regulate gene expression such as enhancers. Identifying associations between enhancers and phenotypes is challenging because enhancer activity can be tissue-dependent and functionally conserved despite low sequence conservation. We developed the Tissue-Aware Conservation Inference Toolkit (TACIT) to associate candidate enhancers with species' phenotypes using predictions from machine learning models trained on specific tissues.

Social adversity during juvenile age but not adulthood increases susceptibility to an immune challenge later in life.

Adverse experiences in early life can increase mental vulnerability to immune challenges experienced later in life, which may induce the development of stress-related psychopathologies. Here, we investigated whether the combined effect of both events is higher if the first adverse experience occurs when the brain is still in development. Therefore, male Wistar rats were exposed to repeated social defeat (RSD, first hit) during juvenile age or adulthood and to an immune challenge consisting of a single injection of lipopolysaccharide (LPS, second hit) in adulthood.

Patient-specific radiological protection precautions following Cs collagen embedded Cs-131 implantation in the brain.

Objective: Cesium-131 brachytherapy is an adjunct for brain tumor treatment, offering potential clinical and radiation protection advantages over other isotopes including iodine-125. We present evidence-based radiation safety recommendations from an initial experience with Cs-131 brachytherapy in the resection cavities of recurrent, previously irradiated brain metastases.

Methods: Twenty-two recurrent brain metastases in 18 patients were resected and treated with permanent Cs-131 brachytherapy implantation using commercially procured seed-impregnated collagen tiles (GammaTile, GT Medical Technologies).

Whole-Genome Duplication Shapes the Aneuploidy Landscape of Human Cancers.

Unlabelled: Aneuploidy is a hallmark of cancer with tissue-specific prevalence patterns that suggest it plays a driving role in cancer initiation and progression. However, the contribution of aneuploidy to tumorigenesis depends on both cellular and genomic contexts. Whole-genome duplication (WGD) is a common macroevolutionary event that occurs in more than 30% of human tumors early in tumorigenesis.

Allosteric Interactions between Adenosine A and Dopamine D Receptors in Heteromeric Complexes: Biochemical and Pharmacological Characteristics, and Opportunities for PET Imaging.

Adenosine and dopamine interact antagonistically in living mammals. These interactions are mediated via adenosine A and dopamine D receptors (R). Stimulation of AR inhibits and blockade of AR enhances DR-mediated locomotor activation and goal-directed behavior in rodents.

Silencing of H4R inhibits the production of IL-1β through SAPK/JNK signaling in human mast cells.

Context: Mast cell (MC) activation through H4R releases various inflammatory mediators which are associated with allergic asthma.

Objectives: To investigate the siRNA-mediated gene silencing effect of H4R on human mast cells (HMCs) functions and the activation of stress-activated protein kinases (SAPK)/jun amino-terminal kinases (JNK) signaling pathways for the release of ineterleukin-1β (IL-1β) in HMCs.

Materials And Methods: H4R expression was analyzed by RT-PCR and western blotting in human mast cell line-1 (HMC-1) cells and H4RsiRNA transfected cells.