The importance of tyrosines in multimers of cyclic RGD nonapeptides: towards αvβ6-integrin targeted radiotherapeutics.

In a recent paper in this journal (, 2023, , 2429), we described an unusually strong impact of regiospecific exchange of phenylalanines by tyrosines in 10 gallium-68-labeled trimers of certain cyclic RGD peptides, c[XRGDLAXp(Me)K] (X = F or Y), on non-specific organ uptakes. We found that there was, in part, no correlation of liver uptake with established polarity proxies, such as the octanol-water distribution coefficient (log ). Since this observation could not be explained straightforwardly, we suggested that the symmetry of the compounds had resulted in a synergistic interaction of certain components of the macromolecules.

Sensitive Positron Emission Tomography Imaging of PD-L1 Expression in Human Breast and Lung Carcinoma Xenografts Using the Radiometalated Peptide Ga-68-TRAP-WL12.

Noninvasive imaging of the immune checkpoint protein programmed death ligand 1 (PD-L1; synonyms: CD274, B7-H1) holds great promise to improve patient selection and, thus, response rates for immune checkpoint therapy (ICT) with monoclonal antibodies targeting the PD1/PD-L1 axis. The PD-L1 specific peptide WL12 (cyclo(AcY-(Me)A-N-P-H-L-Hyp-W-S-W(Me)-(Me)Nle-(Me)Nle-O-C)-G-NH) was functionalized with the Gallium-68 chelator TRAP by means of click chemistry (CuAAC). The resulting conjugate TRAP-WL12 was labeled with Gallium-68 within 16 min, with approximately 90% radiochemical yield and 99% radiochemical purity, affording Ga-68-TRAP-WL12 with molar activities typically exceeding 100 MBq/nmol.

Epidemiology, Risk Factors, and Prophylaxis Use for Pneumonia in the Non-HIV Population: A Retrospective Study in Québec, Canada.

Background: pneumonia (PJP) remains a significant threat in immunocompromised cases. Recent data on epidemiology and risk factors for PJP in non-HIV cases are scarce, and guidelines on appropriate prophylaxis are lacking.

Methods: In this multicenter retrospective trial, all non-HIV adult cases admitted to hospitals in Québec City, Canada, between January 2011 and January 2021 with a diagnosis of PJP were assessed for eligibility.

Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

Purpose: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research.

Complexity of αvβ6-integrin targeting RGD peptide trimers: emergence of non-specific binding by synergistic interaction.

Multimerization is an established strategy to design bioactive macromolecules with enhanced avidity, which has been widely employed to increase the target-specific binding and uptake of imaging probes and pharmaceuticals. However, the factors governing the general biodistribution of multimeric probes are less well understood but are nonetheless decisive for their clinical application. We found that regiospecific exchange of phenylalanine by tyrosine (chemically equivalent to addition of single oxygen atoms) can have an unexpected, dramatic impact on the behavior of gallium-68 labeled αvβ6-integrin binding peptides trimers.