Re-design and evaluation of diclofenac-based carborane-substituted prodrugs and their anti-cancer potential.

In this study, we investigated a novel anti-cancer drug design approach by revisiting diclofenac-based carborane-substituted prodrugs. The redesigned compounds combine the robust carborane scaffold with the oxindole framework, resulting in four carborane-derivatized oxindoles and a unique zwitterionic amidine featuring a nido-cluster. We tested the anti-cancer potential of these prodrugs against murine colon adenocarcinoma (MC38), human colorectal carcinoma (HCT116), and human colorectal adenocarcinoma (HT29).

Enhancing the radionuclide theranostic concept through the radiohybrid approach.

Radionuclide theranostics - a fast-growing emerging field in radiopharmaceutical sciences and nuclear medicine - offers a personalised and precised treatment approach by combining diagnosis with specific and selective targeted endoradiotherapy. This concept is based on the application of the same molecule, labelled with radionuclides possessing complementary imaging and therapeutic properties, respectively. In radionuclide theranostics, radionuclide pairs consisting of the same element, such as Cu/Cu, Pb/Pb or I/I are of significant interest due to their identical chemical and pharmacological characteristics.

Cross-bridged cyclam derivatives with bis(phosphinate) and phosphinate-phosphonate pendant arms (cb-BPC) as chelators for copper radioisotopes.

Copper radioisotopes can be used for imaging as well as for therapy and, thus, can form ideal theranostic pairs. The Cu(II) complexes of cross-bridged cyclam (cb-cyclam) derivatives are considered to be highly stable . However, the complexes are mostly formed under harsh conditions not compatible with sensitive biomolecules.

Synthesis and Preclinical Evaluation of a Bispecific PSMA-617/RM2 Heterodimer Targeting Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) have been used for diagnostic molecular imaging/therapy of prostate cancer (PCa). To address tumor heterogeneity, we synthesized and evaluated a bispecific PSMA/GRPR ligand () combining PSMA-617 () and the GRPR antagonist RM2 () with the radiometal chelator DOTA. was radiolabeled with Ga ([Ga]Ga-) and Lu ([Lu]Lu-).

Combined PET Radiotracer Approach Reveals Insights into Stromal Cell-Induced Metabolic Changes in Pancreatic Cancer In Vitro and In Vivo.

Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach.

Cyclohexanediamine Triazole (CHDT) Functionalization Enables Labeling of Target Molecules with AlF/Ga/In.

The AlF-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of , which allows AlF-labeling already at ambient temperature. While the suitability of for functionalization and radiofluorination of proteins is well established, its use for small molecules or peptides is less explored.

Scalability study on [La]LaCl production with a focus on potential clinical applications.

Background: In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with Ac is still open, and La features attractive radiation properties to claim this place.

Programmable Release of Chemotherapeutics from Ferrocene-Based Injectable Hydrogels Slows Melanoma Growth.

Hydrogel-based injectable drug delivery systems provide temporally and spatially controlled drug release with reduced adverse effects on healthy tissues. Therefore, they represent a promising therapeutic option for unresectable solid tumor entities. In this study, a peptide-starPEG/hyaluronic acid-based physical hydrogel is modified with ferrocene to provide a programmable drug release orchestrated by matrix-drug interaction and local reactive oxygen species (ROS).

Deep learning based bilateral filtering for edge-preserving denoising of respiratory-gated PET.

Background: Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations.

Carborane Conjugates with Ibuprofen, Fenoprofen and Flurbiprofen: Synthesis, Characterization, COX Inhibition Potential and In Vitro Activity.

The most effective anticancer drugs currently entail substantial and formidable side effects, and resistance of tumors to chemotherapeutic agents is a further challenge. Thus, the search for new anticancer drugs as well as novel therapeutic methods is still extremely important. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit COX (cyclooxygenase), overexpressed in some tumors.

Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates.

Discussed are two picolinate appended bispidine ligands (3,7-diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis-pyridine derivative, which are all known to strongly bind Cu.

Chelator impact: investigating the pharmacokinetic behavior of copper-64 labeled PD-L1 radioligands.

Background: Programmed cell death ligand 1 (PD-L1) plays a critical role in the tumor microenvironment and overexpression in several solid cancers has been reported. This was associated with a downregulation of the local immune response, specifically of T-cells. Immune checkpoint inhibitors showed a potential to break this localized immune paralysis, but only 30% of patients are considered responders.

Alpha-Emitting Radionuclides: Current Status and Future Perspectives.

The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress.

Production of the PET radionuclide Cu via the Ni(p,2n)Cu nuclear reaction.

Background: There are only a handful of true theranostic matched pairs, and in particular the theranostic radiocopper trio Cu, Cu and Cu, for diagnosis and therapy respectively, is a very attractive candidate. In fact, the alternative of two imaging radionuclides with different half-lives is a clear advantage over other theranostic pairs, since it offers a better matching for the tracer biological and radionuclide physical half-lives. Due to the high availability of Cu, its translation into the clinic is being successfully carried out, giving the example of the FDA approved radiopharmaceutical Detectnet (copper Cu 64 dotatate injection).

Preclinical evaluation of an F-labeled N-acryloyllysine piperazide for covalent targeting of transglutaminase 2.

Background: Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associated TGase 2, and targeted covalent inhibitors appear to be particularly attractive as vector molecules.

Preparation of F-Labeled Tracers Targeting Fibroblast Activation Protein via Sulfur [F]Fluoride Exchange Reaction.

Early detection and treatment of cancers can significantly increase patient prognosis and enhance the quality of life of affected patients. The emerging significance of the tumor microenvironment (TME) as a new frontier for cancer diagnosis and therapy may be exploited by radiolabeled tracers for diagnostic imaging techniques such as positron emission tomography (PET). Cancer-associated fibroblasts (CAFs) within the TME are identified by biomarkers such as fibroblast activation protein alpha (FAPα), which are expressed on their surfaces.

Combining Cisplatin with Different Radiation Qualities-Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis.

Background: The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin.

Design, Synthesis, and Biological Evaluation of Small-Molecule-Based Radioligands with Improved Pharmacokinetic Properties for Imaging of Programmed Death Ligand 1.

Small molecules offer some advantages for developing positron emission tomography (PET) tracers and are therefore a promising approach for imaging and therapy monitoring of programmed death ligand 1 (PD-L1) positive tumors. Here, we report six biphenyl PD-L1 radioligands using the NODA-GA-chelator for efficient copper-64 complexation. These radioligands contain varying numbers of sulfonic and/or phosphonic acid groups, serving as hydrophilizing units to lower the log value down to -4.

Selecting active matter according to motility in an acoustofluidic setup: self-propelled particles and sperm cells.

Active systems - including sperm cells, living organisms like bacteria, fish, birds, or active soft matter systems like synthetic "microswimmers" - are characterized by motility, , the ability to propel using their own "engine". Motility is the key feature that distinguishes active systems from passive or externally driven systems. In a large ensemble, motility of individual species can vary in a wide range.

Molecular imaging of bacterial outer membrane vesicles based on bacterial surface display.

The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain (E.

Exploring Hydrophilic PD-L1 Radiotracers Utilizing Phosphonic Acids: Insights into Unforeseen Pharmacokinetics.

Immune checkpoint inhibitor therapy targeting the PD-1/PD-L1 axis in cancer patients, is a promising oncological treatment. However, the number of non-responders remains high, causing a burden for the patient and the healthcare system. Consequently, a diagnostic tool to predict treatment outcomes would help with patient stratification.

Methods gold standard in clinic millifluidics multiplexed extended gate field-effect transistor biosensor with gold nanoantennae as signal amplifiers.

We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors.

Exploring the Potential of Nanogels: From Drug Carriers to Radiopharmaceutical Agents.

Nanogels open up access to a wide range of applications and offer among others hopeful approaches for use in the field of biomedicine. This review provides a brief overview of current developments of nanogels in general, particularly in the fields of drug delivery, therapeutic applications, tissue engineering, and sensor systems. Specifically, cyclodextrin (CD)-based nanogels are important because they have exceptional complexation properties and are highly biocompatible.