Novel Chlorin with a HYNIC: Synthesis, Tc-Radiolabeling, and Initial Preclinical Evaluation.

The use of radiopharmaceuticals for diagnostics in oncology allows for the detection of the disease at an early stage. Among diagnostic radionuclides, Tc is a promising isotope that has been used to create several drugs for clinical use. One of the most effective Tc chelators is 6-hydrazinylnicotinic acid (HYNIC), which, when combined with various vector molecules, can be used for targeted delivery of radionuclides to tumor tissues.

Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [Tc]Tc(CO)-(HE)-Ec1 for Visualization of EpCAM-Expressing Lung Cancer.

A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using Tc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection.

Comparative Preclinical Evaluation of HYNIC-Modified Designed Ankyrin Repeat Proteins for the Tc-Based Imaging of HER2-Expressing Malignant Tumors.

HER2 status determination is a necessary step for the proper choice of therapy and selection of patients for the targeted treatment of cancer. Targeted radiotracers such as radiolabeled DARPins provide a noninvasive and effective way for the molecular imaging of HER2 expression. This study aimed to evaluate tumor-targeting properties of three Tc-labeled DARPin G3 variants containing Gly-Gly-Gly-Cys (GC), (Gly-Gly-Gly-Ser)-Cys ((GS)C), or Glu-Glu-Glu-Cys (EC) amino acid linkers at the C-terminus and conjugated to the HYNIC chelating agent, as well as to compare them with the clinically evaluated DARPin G3 labeled with Tc(CO) using the (HE)-tag at the N-terminus.

Preclinical Evaluation of a Novel High-Affinity Radioligand [Tc]Tc-BQ0413 Targeting Prostate-Specific Membrane Antigen (PSMA).

Radionuclide imaging using radiolabeled inhibitors of prostate-specific membrane antigen (PSMA) can be used for the staging of prostate cancer. Previously, we optimized the Glu-urea-Lys binding moiety using a linker structure containing 2-napththyl-L-alanine and L-tyrosine. We have now designed a molecule that contains mercaptoacetyl-triglutamate chelator for labeling with Tc-99m (designated as BQ0413).

Optimal Conservative Therapy Use among Adult Cure Glomerulonephropathy Participants with IgA Nephropathy.

Optimal supportive therapy with BP and proteinuria control is pivotal in treating patients with IgA nephropathy. Suboptimal treatment of hypertension and proteinuria persisted in many patients with IgA nephropathy in the Cure Glomerulonephropathy Network study. Many patients had above-target proteinuria despite optimal BP control and may benefit from novel therapies or clinical trials.

Phase I clinical evaluation of Tc-labeled Affibody molecule for imaging HER2 expression in breast cancer.

The determination of tumor human epidermal growth factor receptor type 2 (HER2) status is of increasing importance with the recent approval of more efficacious HER2-targeted treatments. There is a lack of suitable methods for clinical HER2 expression assessment. Affibody molecules are small affinity proteins ideal for imaging detection of receptors, which are engineered using a small (molecular weight 6.

The Significance of Hematuria in Podocytopathies.

Background: Hematuria is frequently present in podocytopathies, but its significance and prognostic value is not well described in these proteinuric kidney diseases. This study describes the prevalence and association between hematuria and kidney-related outcomes in these disorders.

Methods: Hematuria was assessed at the initial urinalysis in participants with the following podocytopathies-membranous nephropathy, minimal change disease, and FSGS-in the Nephrotic Syndrome Study Network and Cure Glomerulonephropathy cohorts with >24 months of follow-up.

Synthesis, I-Radiolabeling Optimization, and Initial Preclinical Evaluation of Novel Urea-Based PSMA Inhibitors with a Tributylstannyl Prosthetic Group in Their Structures.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide including two phenylalanine residues in the L-configuration as the peptide fragment of the linker, and 3- or 4-(tributylstannyl)benzoic acid as a prosthetic group in their structures for radiolabeling. The standard compounds [I]PSMA-m-IB and [I]PSMA-p-IB for comparative and characterization studies were first synthesized using two alternative synthetic approaches.

The Impact of Caregiving History on Later-Life Self-Perceptions of Aging.

Objectives: Theories suggest that self-perceptions of aging (SPA) reflect structural and cultural ageism together with an individual's personal life experiences. We examine the impact of an individual's history of informal caregiving on their SPA.

Methods: Using data from the Health and Retirement Study (HRS, N = 8,372, age range 50-102 years), we investigated caregiving history as a determinant of later-life SPA.

Intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases: a prospective observational study.

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.

Clinical Course of Adult FSGS and Minimal Change Disease in North American and Japanese Cohorts.

Key Points: Data from different geographical regions highlighted the differences in clinical manifestations and treatment response of adult FSGS/minimal change disease. There were shared factors that were associated with treatment response across the cohorts: FSGS, higher BP, and lower eGFR. Recognizing geographical difference allows us better understanding of disease biology, risk prediction, and design of future clinical trials.

Comparative Preclinical Evaluation of Peptide-Based Chelators for the Labeling of DARPin G3 with Tc for Radionuclide Imaging of HER2 Expression in Cancer.

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [Tc]Tc-(HE)-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)), provided clear imaging of HER2 expressing breast cancer 2-4 h after injection.

Changes in practice patterns in Japan from before to after JSDT 2013 guidelines on hemodialysis prescriptions: results from the JDOPPS.

Background: The Japanese Society for Dialysis Therapy (JSDT) published in 2013 inaugural hemodialysis (HD) guidelines. Specific targets include 1.4 for single-pool Kt/V (spKt/V) with a minimum dose of 1.

Influence of the Position and Composition of Radiometals and Radioiodine Labels on Imaging of Epcam Expression in Prostate Cancer Model Using the DARPin Ec1.

The epithelial cell adhesion molecule (EpCAM) is intensively overexpressed in 40-60% of prostate cancer (PCa) cases and can be used as a target for the delivery of drugs and toxins. The designed ankyrin repeat protein (DARPin) Ec1 has a high affinity to EpCAM (68 pM) and a small size (18 kDa). Radiolabeled Ec1 might be used as a companion diagnostic for the selection of PCa patients for therapy.

Radiolabeled Complex of Antimicrobial Peptides UBI29-41 and UBI18-35 Labeled with Tc for Differential Diagnosis of Bone Infection of the Limbs.

We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes Тс-DPAH-UBI29-41 and Тс-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%.

International variation in dialysis discontinuation in patients with advanced kidney disease.

Background: Decisions about dialysis for advanced kidney disease are often strongly shaped by sociocultural and system-level factors rather than the priorities and values of individual patients. We examined international variation in the uptake of conservative approaches to the care of patients with advanced kidney disease, in particular discontinuation of dialysis.

Methods: We employed an observational cohort study design using data collected from patients maintained on long-term hemodialysis between 1996 and 2015 in facilities across 12 developed countries participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Early-life Health as a Lifelong Precursor of Self-Related Views of Aging in Later Life.

Objectives: Age stereotypes and expectations about one's own aging commence in childhood but most research focuses on predictive associations with midlife health behaviors, later-life chronic conditions, biomarkers, and longevity. Surprisingly little is known about the role of poor childhood health in these associations. This study aims to fill this gap.

Single cell transcriptomics identifies focal segmental glomerulosclerosis remission endothelial biomarker.

To define cellular mechanisms underlying kidney function and failure, the KPMP analyzes biopsy tissue in a multicenter research network to build cell-level process maps of the kidney. This study aimed to establish a single cell RNA sequencing strategy to use cell-level transcriptional profiles from kidney biopsies in KPMP to define molecular subtypes in glomerular diseases. Using multiple sources of adult human kidney reference tissue samples, 22,268 single cell profiles passed KPMP quality control parameters.

Long-term autobiographical memory across middle childhood: patterns, predictors, and implications for conceptualizations of childhood amnesia.

We examined recall of events by children 4-11 years to inform patterns of retention of autobiographical memories as well as factors that predict their survival. 101 children participated in a 4-year prospective study. At study inception, children were 4, 6, and 8 years.

Missed Hemodialysis Treatments: International Variation, Predictors, and Outcomes in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Rationale & Objective: Missed hemodialysis (HD) treatments not due to hospitalization have been associated with poor clinical outcomes and related in part to treatment nonadherence. Using data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 5 (2012-2015), we report findings from an international investigation of missed treatments among patients prescribed thrice-weekly HD.

Study Design: Prospective observational study.

Evaluating the effectiveness of IV iron dosing for anemia management in common clinical practice: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Background: Anemia management protocols in hemodialysis (HD) units differ conspicuously regarding optimal intravenous (IV) iron dosing; consequently, patients receive markedly different cumulative exposures to IV iron and erythropoiesis-stimulating agents (ESAs). Complementary to IV iron safety studies, our goal was to gain insight into optimal IV iron dosing by estimating the effects of IV iron doses on Hgb, TSAT, ferritin, and ESA dose in common clinical practice.

Methods: 9,471 HD patients (11 countries, 2009-2011) in the DOPPS, a prospective cohort study, were analyzed.

Predictors of age-related and individual variability in autobiographical memory in childhood.

Development of autobiographical memory is as a gradual process beginning in early childhood and continuing through late adolescence. Substantial attention has been paid to early childhood when first personal memories are formed; less attention has been focused on the flourishing of memories from the late preschool years onward. We addressed this void with a three-year cohort-sequential study of age-related changes in the length, completeness, and coherence of autobiographical narratives by children 4-10 years.