A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides.

Purpose: The angiotensin converting enzyme-2 (ACE2)-entry receptor of SARS-CoV-2-and its homologue, the angiotensin-converting enzyme (ACE), play a pivotal role in maintaining cardiovascular homeostasis. Potential changes in ACE2 expression levels and dynamics after SARS-CoV-2 infection have been barely investigated. The aim of this study was to develop an ACE2-targeting imaging agent as a noninvasive imaging tool to determine ACE2 regulation.

Implementing subtype-specific pre-clinical models of breast cancer to study pre-treatment aspirin effects.

Backgorund: Prior data suggest pre-diagnostic aspirin use impacts breast tumour biology and patient outcome. Here, we employed faithful surgical resection models of HER2+ and triple-negative breast cancer (TNBC), to study outcome and response mechanisms across breast cancer subtypes.

Method: NOD/SCID mice were implanted with HER2+ MDA-MB-231/LN/2-4/H2N, trastuzumab-resistant HER2+ HCC1954 or a TNBC patient-derived xenograft (PDX).

[Dramatic changes in the age structure for medical specialists in the field of mental health].

Background: Over the past 20 years the importance of treatment of people with mental and neurological disorders has greatly increased. Parallel to this development it has become more difficult to attract young physicians to this field. The aim of this study was to examine the development of the number of physicians specialized in the care of patients suffering from neurological, mental and psychosomatic disorders with special consideration of the age structure.

Simultaneous Visualization of Tb- and Lu-Labeled Somatostatin Analogues Using Dual-Isotope SPECT Imaging.

The decay of terbium-161 results in the emission of β¯-particles as well as conversion and Auger electrons, which makes terbium-161 interesting for therapeutic purposes. The aim of this study was to use dual-isotope SPECT imaging in order to demonstrate visually that terbium-161 and lutetium-177 are interchangeable without compromising the pharmacokinetic profile of the radiopharmaceutical. The Tb- and Lu-labeled somatostatin (SST) analogues DOTATOC (agonist) and DOTA-LM3 (antagonist) were tested in vitro to demonstrate equal properties regarding distribution coefficients and cell uptake into SST receptor-positive AR42J tumor cells.

Identification of a PET Radiotracer for Imaging of the Folate Receptor-α: A Potential Tool to Select Patients for Targeted Tumor Therapy.

The aim of this study was to identify a folate receptor-α (FRα)-selective PET agent potentially suitable for the selection of patients who might profit from FRα-targeted therapies. The 6 and 6 isomers of F-aza-5-methyltetrahydrofolate (MTHF) were assessed regarding their binding to FRα and FRβ, expressed on cancer and inflammatory cells, respectively, and compared with F-AzaFol, the folic acid-based analog. FR selectivity was investigated using FRα-transfected (RT16) and FRβ-transfected (D4) CHO cells.

Promising potential of [Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy-a preclinical study using a syngeneic breast cancer model.

Purpose: It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy.

Methods: In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [Lu]Lu-DOTA-folate.

Combined Application of Albumin-Binding [Lu]Lu-PSMA-ALB-56 and Fast-Cleared PSMA Inhibitors: Optimization of the Pharmacokinetics.

The strategy of using radioligands for targeting the prostate-specific membrane antigen (PSMA) revealed to be promising for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Recently developed albumin-binding PSMA radioligands showed a remarkably increased tumor uptake because of the enhanced blood circulation, but higher accumulation of activity was also observed in off-target organs and tissues. The aim of this study was to investigate the option of using fast-cleared, small-molecular-weight PSMA inhibitors (PSMA-11, 2-PMPA, and ZJ-43) to reduce the kidney uptake of [Lu]Lu-PSMA-ALB-56, a previously developed albumin-binding PSMA radioligand.

[Recommendations on performing polygraphy or polysomnography in the fields of psychiatry and psychotherapy : Position paper of the working group on sleep medicine of the German Association for Psychiatry, Psychotherapy and Psychosomatics].

Difficulties in falling asleep and maintaining sleep, nonrestorative sleep and decreased daytime wakefulness represent very common but relatively unspecific health complaints. Around 100 specific sleep-related disorders will be classified in their own major chap. 7 (sleep wake disorders) for the first time in the upcoming 11th version of the International Classification of Diseases (ICD 11).

F-AzaFol for Detection of Folate Receptor-β Positive Macrophages in Experimental Interstitial Lung Disease-A Proof-of-Concept Study.

Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-β is expressed on activated, but not resting macrophages which play a key role in dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for the specific detection of macrophage-driven pathophysiologic processes in experimental ILD.

Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2.

Objective: To evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD).

Methods: The pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting Lu-DOTA-RGD and the SSTR2-targeting Lu-DOTA-NOC radiotracer.

In Vivo Labeling of Plasma Proteins for Imaging of Enhanced Vascular Permeability in the Lungs.

Increased vascular permeability is an important hallmark of many diseases, including cancer, cerebral ischemia, and severe inflammatory disorders. In this regard, the noninvasive assessment of pathologically increased vascular permeability in vivo is of great interest. In this study, the potential of albumin- and transthyretin-binding radioligands was evaluated for imaging of vascular hyperpermeability.

Combination of lutetium-177 labelled anti-L1CAM antibody chCE7 with the clinically relevant protein kinase inhibitor MK1775: a novel combination against human ovarian carcinoma.

Background: Protein kinase inhibitors (PKIs) are currently tested in clinical studies (phase I-III) as an alternative strategy against (recurrent) ovarian cancer. Besides their anti-tumour efficacy, several PKIs have also shown radiosensitizing effects when combined with external beam radiation. Based on these results we asked if the addition of PKIs offers a therapeutic opportunity to improve radioimmunotherapy (RIT) against ovarian cancer.

Combining Albumin-Binding Properties and Interaction with Pemetrexed to Improve the Tissue Distribution of Radiofolates.

Folic-acid-based radioconjugates have been developed for nuclear imaging of folate receptor (FR)-positive tumors; however, high renal uptake was unfavorable in view of a therapeutic application. Previously, it was shown that pre-injection of pemetrexed (PMX) increased the tumor-to-kidney ratio of radiofolates several-fold. In this study, PMX was combined with the currently best performing radiofolate ([Lu]cm13), which is outfitted with an albumin-binding entity.

[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders].

Background: Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders.

Folate Receptor-Positive Gynecological Cancer Cells: In Vitro and In Vivo Characterization.

The folate receptor (FR) is expressed in a variety of gynecological cancer types. It has been widely used for tumor targeting with folic acid conjugates of diagnostic and therapeutic probes. The cervical KB tumor cells have evolved as the standard model for preclinical investigations of folate-based (radio) conjugates.

Living in the Fast Lane: Evidence for a Global Perceptual Timing Deficit in Childhood ADHD Caused by Distinct but Partially Overlapping Task-Dependent Cognitive Mechanisms.

Dysfunctions in perceptual timing have been reported in children with ADHD, but so far only from studies that have not used the whole set of timing paradigms available from the literature, with the diversity of findings complicating the development of a unified model of timing dysfunctions and its determinants in ADHD. Therefore, we employed a comprehensive set of paradigms (time discrimination, time estimation, time production, and time reproduction) in order to explore the perceptual timing deficit profile in our ADHD sample. Moreover, we aimed to detect predictors responsible for timing task performance deficits in children with ADHD and how the timing deficits might be positively affected by methylphenidate.

Evaluation of the first Sc-labeled Affibody molecule for imaging of HER2-expressing tumors.

Introduction: Affibody molecules are small (58 amino acids) high-affinity proteins based on a tri-helix non-immunoglobulin scaffold. A clinical study has demonstrated that PET imaging using Affibody molecules labeled with Ga (T=68min) can visualize metastases of breast cancer expressing human epidermal growth factor receptor type 2 (HER2) and provide discrimination between tumors with high and low expression level. This may help to identify breast cancer patients benefiting from HER2-targeting therapies.

[Insomnia Between Neuro- and Social Sciences - A Psycho-Socio-Somatic Outview].

Insomnia is one of the most prevalent neuropsychiatric disorders throughout Europe. It is associated with a number of health-relevant problems including an increased risk of psychiatric and organic disorders. A variety of organic, social and psychological risk factors takes part in the genesis of these sleep disturbances.

Electronic media use and insomnia complaints in German adolescents: gender differences in use patterns and sleep problems.

Electronic media play an important role in the everyday lives of children and adolescents and have been shown to be associated with sleep problems. The objective of this study was to assess the associations between time spent using different electronic media and insomnia complaints (IC) in German adolescents with particular respect to gender differences in use patterns and associations with IC. Cross-sectional data of a weighted total of 7533 adolescents aged 11-17 stem from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS study) that was conducted from 2003 to 2006.

Sleep-dependent memory consolidation and its implications for psychiatry.

Both sleep disturbance and memory impairment are very common in psychiatric disorders. Since sleep has been shown to play a role in the process of transferring newly acquired information into long-term memory, i.e.

Altered serum fatty acid composition in geriatric depression.

Fatty acids (FA), mainly polyunsaturated (PUFA) of n-3 or n-6 types, may influence neuropsychobiological processes. Decreased levels of n-3 PUFA have been shown to be related to major depression and supplementation of n-3 PUFA seems to contribute to improved depression treatment outcome. The profiles of serum FA profiles in patients with geriatric depression have not been thoroughly studied yet.

Successful physical exercise-induced weight loss is modulated by habitual sleep duration in the elderly: results of a pilot study.

Although it is widely accepted that physical exercise promotes weight loss, physical exercise alone had been found to result in only marginal weight loss compared to no treatment. Interestingly, both subjective and objective sleep duration have been shown to be negatively correlated to the body mass index (BMI). Despite this growing evidence of a relation between sleep duration and body weight, the role of habitual sleep duration in physical exercise-induced weight loss has not been studied so far.

Insomnia complaints and substance use in German adolescents: did we underestimate the role of coffee consumption? Results of the KiGGS study.

The purpose of the study was to study the associations of tobacco, alcohol, marijuana, and coffee use and insomnia complaints (IC) in adolescents with special consideration of the influence of coffee consumption on these relationships. 7698 Subjects aged 11-17 years were investigated in a cross-sectional study within the German Health Interview and Examination Survey for Children and Adolescents. Self-report questionnaires were distributed to the participants.

Paclitaxel improved anti-L1CAM lutetium-177 radioimmunotherapy in an ovarian cancer xenograft model.

Background: Today's standard treatment of advanced-stage ovarian cancer, including surgery followed by a paclitaxel-platinum-based chemotherapy, is limited in efficacy. Recently, we could show that radioimmunotherapy (RIT) with (177)Lu-labelled anti-L1 cell adhesion molecule (L1CAM) monoclonal antibody chCE7 is effective in ovarian cancer therapy. We investigated if the efficacy of anti-L1CAM RIT can be further improved by its combination with paclitaxel (PTX).