Naphtho[1,2-][1,4]diazepinedione-Based P2X4 Receptor Antagonists from Structure-Activity Relationship Studies toward PET Tracer Development.

The P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based P2X4 receptor antagonists aimed at both therapeutic applications and potential use as PET tracers for imaging P2X4 receptor expression in cancer. Structure-activity relationship studies aided by docking studies and molecular dynamics simulations led to a series of compounds with potent P2X4 receptor antagonism, promising inhibition of interleukin-1β release in THP-1 cells and suitability for radiolabeling with fluorine-18.

FAP-Targeted SPECT/CT and PET/CT Imaging for Breast Cancer Patients.

Breast cancer presents a significant global health challenge, necessitating continued innovation in diagnostic and therapeutic approaches. Recent advances have led to the identification of cancer-associated fibroblasts, which are highly prevalent in breast cancers and express fibroblast activation proteins (FAPs), as critical targets. FAP-specific radiotracers, when used with PET/CT and SPECT/CT, have significant potential for improving early breast cancer detection, staging, treatment response monitoring, and therapeutic intervention.

Additional Value of Pertechnetate Scintigraphy to American College of Radiology Thyroid Imaging Reporting and Data Systems and European Thyroid Imaging Reporting and Data Systems for Thyroid Nodule Classification in Euthyroid Patients.

Thyroid nodules are common yet remain a diagnostic challenge. While ultrasound and Thyroid Imaging Reporting and Data Systems (TIRADS) are accepted as standard, the use of thyroid scintigraphy in euthyroid patients is debated. The European Association of Nuclear Medicine advocates it, whereas the American Thyroid Association and European Thyroid Association do not.

Joint estimation of activity, attenuation and motion in respiratory-self-gated time-of-flight PET.

Motivation: Whole-body Positron Emission Tomography (PET) imaging is often hindered by respiratory motion during acquisition, causing significant degradation in the quality of reconstructed activity images. An additional challenge in PET/CT imaging arises from the respiratory phase mismatch between CT-based attenuation correction and PET acquisition, leading to attenuation artifacts. To address these issues, we propose two new, purely data-driven methods for the joint estimation of activity, attenuation, and motion in respiratory self-gated time-of-flight (TOF) PET.

Toolbox of Clickable Benzylguanines for Labeling of HoxB8-Derived Macrophages via SNAP-Tag and Bioorthogonal Chemistry.

Inflammation is a dynamic process which importantly involves migration of immune cells. Understanding the onset, acute phase and resolution of inflammation is greatly facilitated by their imaging. However, immune cells are sensitive, difficult to genetically manipulate and prone to changes in response to contact, hindering the application of well-established cell labeling methods.

Direct specification of lymphatic endothelium from mesenchymal progenitors.

During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state.

Piperazine-based P2X4 receptor antagonists.

The P2X4 receptor (P2X4R), a ligand-gated ion channel activated by ATP, plays a critical role in neuroinflammation, chronic pain, and cancer progression, making it a promising therapeutic target. In this study, we explored the design and synthesis of piperazine-based P2X4R antagonists, building on the structural framework of paroxetine. A series of over 35 compounds were synthesized to investigate structure-activity relationships (SARs) in a Ca²⁺-flux assay for P2X4R antagonistic activity.

Phenol (bio)isosteres in drug design and development.

Due to their versatile properties, phenolic compounds are integral to various biologically active molecules, including many pharmaceuticals. However, their application in drug design is often hindered by issues such as poor oral bioavailability, rapid metabolism, and potential toxicity. This review explores the use of phenol bioisosteres-structurally similar compounds that can mimic the biological activity of phenols while potentially offering improved drug-like properties.

Exploring P2X receptor activity: A journey from cellular impact to electrophysiological profiling.

The development of in vitro pharmacological assays relies on creating genetically modified cell lines that overexpress the target protein of interest. However, the choice of the host cell line can significantly impact the experimental outcomes. This study explores the functional characterization of P2X7 and P2X4 receptor modulators through cellular assays and advanced electrophysiological techniques.

18F-labelled gentiobiose as potential PET-radiotracer for specific bacterial imaging: precursor synthesis, radiolabelling and in vitro evaluation.

Aim: Bacterial infections are a clinical challenge, requiring fast and specific diagnosis to ensure effective treatment. Therefore, this project is dedicated to development of positron emission tomography (PET) radiotracers specifically targeting bacteria. Unlike previously developed bacteria-specific radiotracers, which are successful in detecting Gram-negative bacteria, tracers capable of imaging Gram-positive infections are still lacking.

Combining poly-epitope MoonTags and labeled nanobodies for signal amplification in cell-specific PET imaging in vivo.

Immunorecognition provides an excellent basis for targeted imaging techniques covering a wide range from basic research to diagnostics and from single cells to whole organisms. Fluorescence- or radioisotope-labeled antibodies, antibody fragments or nanobodies enable a direct signal readout upon binding and allow for versatile imaging from microscopy to whole-body imaging. However, as the signal intensity directly correlates with the number of labeled antibodies bound to their epitopes (1:1 binding), sensitivity for low-expressing epitopes can be limiting for visualization.

Which Comprehensive Geriatric Assessment (CGA) instruments are currently used in Germany: a survey.

Background: The Comprehensive Geriatric Assessment (CGA) records geriatric syndromes in a standardized manner, allowing individualized treatment tailored to the patient's needs and resources. Its use has shown a beneficial effect on the functional outcome and survival of geriatric patients. A recently published German S1 guideline for level 2 CGA provides recommendations for the use of a broad variety of different assessment instruments for each geriatric syndrome.

Synthesis, radiosynthesis and biochemical evaluation of fluorinated analogues of sphingosine-1-phosphate receptor 3 specific antagonists using PET.

Sphingosine-1-phosphate and its receptors (S1PRs) are involved in several diseases such as auto immunity, inflammation and cardiovascular disorders. The S1P analogue fingolimod (Gilenya®) is currently in use for the treatment of relapsing multiple sclerosis. S1PRs are also promising targets for clinical molecular imaging in vivo.

Dual Emissive Zn(II) Naphthalocyanines: Synthesis, Structural and Photophysical Characterization with Theory-Supported Insights towards Soluble Coordination Compounds with Visible and Near-Infrared Emission.

Metal phthalocyaninates and their higher homologues are recognized as deep-red luminophores emitting from their lowest excited singlet state. Herein, we report on the design, synthesis, and in-depth characterization of a new class of dual-emissive (visible and NIR) metal naphthalocyaninates. A 4-,-dimethylaminophen-4-yl-substituted naphthalocyaninato zinc(II) complex () and the derived water-soluble coordination compound () exhibit a near-infrared fluorescence from the lowest ligand-centered state, along with a unique push-pull-supported luminescence in the visible region of the electromagnetic spectrum.

Genetically Encoded Reporters to Monitor Hypoxia.

Hypoxia resulting from an imbalance of oxygen availability and consumption defines a metabolic cellular state with a profound impact on developmental processes, tissue maintenance, and the development of pathologies. Fluorescence imaging using genetically encoded reporters enables hypoxia and oxygen imaging with cellular resolution. Thereby unrestricted visualization of hypoxic cells and regions essentially relies on the availability of oxygen-independent fluorescent proteins like UnaG, isolated from the Japanese freshwater eel.

Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction.

Glioblastoma presents characteristically with an exuberant, poorly functional vasculature that causes malperfusion, hypoxia and necrosis. Despite limited clinical efficacy, anti-angiogenesis resulting in vascular normalization remains a promising therapeutic approach. Yet, fundamental questions concerning anti-angiogenic therapy remain unanswered, partly due to the scale and resolution gap between microscopy and clinical imaging and a lack of quantitative data readouts.

Diagnostic Performance of [F]TFB PET/CT Compared with Therapeutic Activity [I]Iodine SPECT/CT and [F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma.

[F]tetrafluoroborate ([F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)-based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [F]TFB PET with high-activity posttherapeutic [I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [F]FDG PET/CT in suspected dedifferentiation. Twenty-six patients treated with high-activity radioactive [I]iodine therapy (range, 5.

Infection Imaging: Focus on New Tracers?

Infections account for relevant morbidity and mortality, especially if the cardiovascular system is affected. Clinical manifestations are often unspecific, resulting in a challenging diagnostic work-up. The use of molecular imaging methods, namely [F]FDG PET and leukocyte scintigraphy, is increasingly recognized in recently published international guidelines.