The heterobivalent (SSTR2/albumin) radioligand [Cu]Cu-NODAGA-cLAB4-TATE enables efficient somatostatin receptor radionuclide theranostics.

Somatostatin type 2 receptor (SSTR2) radionuclide therapy using β particle-emitting radioligands has entered clinical practice for the treatment of neuroendocrine neoplasms (NENs). Despite the initial success of [Lu]Lu‑DOTA-TATE, theranostic SSTR2 radioligands require improved pharmacokinetics and enhanced compatibility with alternative radionuclides. Consequently, this study evaluates the pharmacokinetic effects of the albumin-binding domain cLAB4 on theranostic performance of copper‑67-labeled NODAGA-TATE variants in an SSTR2-positive mouse pheochromocytoma (MPC) model.

A web-based knowledge database to provide evidence-based information to cancer patients: Utilization within the PIKKO study.

Purpose: Cancer is associated with an urgent need for understandable and reliable information, which is often not satisfied by information available online. Therefore, as part of the PIKKO project, a web-based knowledge database (WDB) was introduced to provide cancer patients with quality-assured, evidence-based information. This paper aims to provide insights into the usage (Who? How? What?) and the effects regarding health literacy of the WDB.

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).

COVID-19-associated costs and mortality in Germany: an incidence-based analysis from a payer's perspective.

Background: This study aims to estimate average COVID-19-associated healthcare costs per capita in Germany from a payer perspective. In addition, insights into COVID-19-associated mortality should be gained.

Methods: For this purpose, a retrospective longitudinal analysis using health insurance claims data was performed.

Comparative Saturation Binding Analysis of Cu-Labeled Somatostatin Analogues Using Cell Homogenates and Intact Cells.

The development of novel ligands for G-protein-coupled receptors (GPCRs) typically entails the characterization of their binding affinity, which is often performed with radioligands in a competition or saturation binding assay format. Since GPCRs are transmembrane proteins, receptor samples for binding assays are prepared from tissue sections, cell membranes, cell homogenates, or intact cells. As part of our investigations on modulating the pharmacokinetics of radiolabeled peptides for improved theranostic targeting of neuroendocrine tumors with a high abundance of the somatostatin receptor sub-type 2 (SST), we characterized a series of Cu-labeled [Tyr]octreotate (TATE) derivatives in vitro in saturation binding assays.

The impact of the COVID-19 pandemic restrictions on the health care utilization of cancer patients.

Background: COVID-19 has impacted both society and medical care. While Germany entered the first lockdown in spring 2020, the PIKKO study (Patient information, communication and competence empowerment in oncology) was still active. The intervention modules, patient navigator (PN), services of the Saarland Cancer Society (SCS), psycho-social counseling and different courses, and online knowledge database (ODB) continued to be offered, but in an adapted form.

Patient information, communication and competence empowerment in oncology: Results and learnings from the PIKKO study.

Purpose: Many concepts for accompanying and supporting cancer patients exist and have been studied over time. One of them was PIKKO (a German acronym for "Patient information, communication and competence empowerment in oncology"), which combined a patient navigator, socio-legal and psychological counseling (with psychooncologists), courses dealing with various supportive aspects, and a knowledge database with validated and easy-to-understand disease-related information. The aim was to increase the patients' health-related quality of life (HRQoL), self-efficacy as well as health literacy and to reduce psychological complaints such as depression and anxiety.

[Psychometric Properties of the Qualiskope-A for Measuring Patient Satisfaction with Outpatient Medical Treatment: Use in Oncology and Transferability to Inpatient Care].

Aim: The Qualiskope-A is a German-language PREM (Patient Reported Experience Measure) which, with the help of 27 items allocated to four scales, enables measurement of patient satisfaction with outpatient medical treatment along four dimensions of patient satisfaction. This study examined whether the questionnaire delivers reliable results in an oncological population and whether its application can be extended to inpatient care.

Method: Required data was collected as part of the PIKKO study.

Enzymological Characterization of Cu-Labeled Neprilysin Substrates and Their Application for Modulating the Renal Clearance of Targeted Radiopharmaceuticals.

The applicability of radioligands for targeted endoradionuclide therapy is limited due to radiation-induced toxicity to healthy tissues, in particular to the kidneys as primary organs of elimination. The targeting of enzymes of the renal brush border membrane by cleavable linkers that permit the formation of fast eliminating radionuclide-carrying cleavage fragments gains increasing interest. Herein, we synthesized a small library of Cu-labeled cleavable linkers and quantified their substrate potentials toward neprilysin (NEP), a highly abundant peptidase at the renal brush border membrane.

Modulating the pharmacokinetic profile of Actinium-225-labeled macropa-derived radioconjugates by dual targeting of PSMA and albumin.

Small Ac-labeled prostate-specific membrane antigen (PSMA)-targeted radioconjugates have been described for targeted alpha therapy of metastatic castration-resistant prostate cancer. Transient binding to serum albumin as a highly abundant, inherent transport protein represents a commonly applied strategy to modulate the tissue distribution profile of such low-molecular-weight radiotherapeutics and to enhance radioactivity uptake into tumor lesions with the ultimate objective of improved therapeutic outcome. Two ligands and were synthesized by combining a macropa-derived chelator with either one or two lysine-ureido-glutamate-based PSMA- and 4-(-iodophenyl)butyrate albumin-binding entities using multistep peptide-coupling chemistry.

Toward Personalized Medicine: One Chelator for Imaging and Therapy with Lutetium-177 and Actinium-225.

We report a nonadentate bispidine (3,7-diazabicyclo[3.3.1]nonane) that unveils the potential to bind theranostically relevant radionuclides, including indium-111, lutetium-177, and actinium-225 under mild labeling conditions.

Exploring Nitric Oxide (NO)-Releasing Celecoxib Derivatives as Modulators of Radioresponse in Pheochromocytoma Cells.

COX-2 can be considered as a clinically relevant molecular target for adjuvant, in particular radiosensitizing treatments. In this regard, using selective COX-2 inhibitors, e.g.

Nanosensors in clinical development of CAR-T cell immunotherapy.

Immunotherapy using CAR-T cells is a new technological paradigm for cancer treatment. To avoid severe side effects and tumor escape variants observed for conventional CAR-T cells approach, adaptor CAR technologies are under development, where intermediate target modules redirect immune cells against cancer. In this work, silicon nanowire field-effect transistors are used to develop target modules for an optimized CAR-T cell operation.

"Clickable" Albumin Binders for Modulating the Tumor Uptake of Targeted Radiopharmaceuticals.

The intentional binding of radioligands to albumin gains increasing attention in the context of radiopharmaceutical cancer therapy as it can lead to an enhanced radioactivity uptake into the tumor lesions and, thus, to a potentially improved therapeutic outcome. However, the influence of the radioligand's albumin-binding affinity on the time profile of tumor uptake has been only partly addressed so far. Based on the previously identified -4-(4-iodophenyl)butanoyl-lysine scaffold, we designed "clickable" lysine-derived albumin binders (cLABs) and determined their dissociation constants toward albumin by novel assay methods.

Correlation between the Incontinence Severity Index (ISI) and the quality of life dimensions of the King's Health Questionnaire (KHQ) in German-speaking urinary incontinent women.

Background: The Incontinence Severity Index (ISI) is a patient questionnaire to ascertain severity of urinary incontinence (UI) via two items. The aim of this study was to translate the ISI into German, to compare it with the German-language King's Health Questionnaire (KHQ), an already validated German-language questionnaire within the scope of UI to measure condition-specific quality of life (QoL), and to gain more insights into association between symptom severity and QoL in German-speaking women affected.

Methods: A total of 161 urinary incontinent women completed the ISI and the KHQ.

Psychometric properties of the German-language questionnaire for urinary incontinence diagnosis (QUID) in women with urinary incontinence.

Purpose: The aim of this study was to translate the questionnaire for urinary incontinence diagnosis (QUID) into German and to assess its psychometric properties in German-speaking women with urinary incontinence (UI). The QUID contains two subscales to measure symptom severity of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) and to distinguish between both forms.

Methods: A total of 161 women with UI completed the QUID and the King's Health Questionnaire (KHQ), each in the German version.

Patient information, communication and competence empowerment in oncology (PIKKO) - evaluation of a supportive care intervention for overall oncological patients. Study protocol of a non-randomized controlled trial.

Background: Cancer patients have to undergo a difficult medical therapy and are also confronted with various psychological, social and economic problems. Support is available from many providers, but patients often gain no access to it. Accordingly, there is a need for a single point of contact that can provide advice, information and assistance.

Measuring azimuthal and radial modes of photons.

With the emergence of the field of quantum communications, the appropriate choice of photonic degrees of freedom used for encoding information is of paramount importance. Highly precise techniques for measuring the polarisation, frequency, and arrival time of a photon have been developed. However, the transverse spatial degree of freedom still lacks a measurement scheme that allows the reconstruction of its full transverse structure with a simple implementation and a high level of accuracy.

Structure and 3D arrangement of endoplasmic reticulum membrane-associated ribosomes.

In eukaryotic cells, cotranslational protein translocation across the endoplasmic reticulum (ER) membrane requires an elaborate macromolecular machinery. While structural details of ribosomes bound to purified and solubilized constituents of the translocon have been elucidated in recent years, little structural knowledge of ribosomes bound to the complete ER protein translocation machinery in a native membrane environment exists. Here, we used cryoelectron tomography to provide a three-dimensional reconstruction of 80S ribosomes attached to functional canine pancreatic ER microsomes in situ.

The three-dimensional organization of polyribosomes in intact human cells.

Structural studies have provided detailed insights into different functional states of the ribosome and its interaction with factors involved in nascent peptide folding, processing, and targeting. However, how the translational machinery is organized spatially in native cellular environments is not yet well understood. Here we have mapped individual ribosomes in electron tomograms of intact human cells by template matching and determined the average structure of the ribosome in situ.

Structure of hibernating ribosomes studied by cryoelectron tomography in vitro and in situ.

Ribosomes arranged in pairs (100S) have been related with nutritional stress response and are believed to represent a "hibernation state." Several proteins have been identified that are associated with 100S ribosomes but their spatial organization has hitherto not been characterized. We have used cryoelectron tomography to reveal the three-dimensional configuration of 100S ribosomes isolated from starved Escherichia coli cells and we have described their mode of interaction.

The non-canonical Hop protein from Caenorhabditis elegans exerts essential functions and forms binary complexes with either Hsc70 or Hsp90.

Heat shock protein (Hsp) 70/Hsp90-organizing proteins (Hop/Sti1) are thought to function as adaptor proteins to link the two chaperone machineries Hsp70 and Hsp90 during the processing of substrate proteins in eukaryotes. Hop (Hsp70/Hsp90-organizing protein) is composed of three tetratricopeptide repeat (TPR) domains, of which the first (TPR1) binds to Hsp70, the second (TPR2A) binds to Hsp90, and the third (TPR2B) is of unknown function. Contrary to most other eukaryotes, the homologue closest to the Caenorhabditis elegans Hop homologue R09E12.