Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis

The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of ¹⁷⁷Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT.     

Mass‐transfer enhancement by a reversible chemical reaction across the interface of a bubble rising under Stokes flow

Mass transfer around a bubble rising in a liquid under Stokes regime is investigated when a reversible chemical reaction, , is taken into account. Four dimensionless parameters control the interfacial transfer rate: the Péclet and Damköhler numbers, the ratio of the diffusion coefficient of both species, and the reaction equilibrium constant. The mass‐transfer equations are solved numerically with a finite element technique. A boundary layer approach is also proposed and solved with a coupled technique of finite difference and Chebyshev‐spectral method. The equilibrium constant and the ratio of diffusion coefficients have a strong influence on the coupling between the chemical reaction and mass transfer leading to an increase of the Sherwood number. The interaction between the chemical reaction and advection is clearly established by the simulations. Conditions corresponding to Péclet number larger than the Damköhler number reduces the effect of the chemical reaction. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3376–3388, 2014     

Novel Heterobimetallic Radiotheranostic: Preparation,Activity, and Biodistribution

A novel Ru^II(arene) theranostic complex is presented. It is based on a 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of ¹⁵³Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at the phosphorus atom despite the presence of other functionalities that are prone to metal coordination. Subsequent labeling with radionuclides such as ¹⁵³Sm can then be performed easily. The resulting heterobimetallic complex exhibits favorable solubility and stability properties in biologically relevant media. It also shows in vitro cytotoxicity in line with that expected for this type of metallodrug, and is nontoxic to the organism as a whole. As a proof of concept, initial studies in healthy mice were performed to obtain information about the uptake, biodistribution, and excretion of the radiolabeled complex.     

Sub-micrometer particulate air pollution and cardiovascular mortality in Beijing, China

Background

While the link between particulate matter and cardiovascular mortality is well established, it is not fully investigated and understood which properties of the aerosol might be responsible for the health effects, especially in polluted mega-city areas.

Objectives

Our goal was to explore the association between daily cardiovascular mortality and different particle metrics in the sub-micrometer range in Beijing, China.

Methods

We obtained daily counts of cause-specific cardiovascular deaths in the Beijing urban area for the period March 2004 to August 2005. Concurrently, continuous measurements of particle number size distributions were performed. Particle number concentrations (NC) between 0.003 μm and 0.8 μm were converted to particle mass and surface area concentrations assuming spherical particles. Semi-parametric Poisson regression models adjusting for trend, seasonality, day of the week, and meteorology were used to estimate immediate, delayed and cumulative particle effects. Additionally, effect modification by air mass origin was investigated.

Results

We observed associations between daily cardiovascular mortality and particle NC for a 2-days delay. Moreover, nearly all particle metrics showed 2-days delayed associations with ischemic heart disease mortality. The strongest association was found for particle NC in the size range 0.03-0.1 μm (7.1% increase in daily mortality with a 95%-confidence interval of 2.9%-11.5%, per an increase of 6250 particles/cm³). Results for surface and mass concentrations with a lag of two days indicated effect modification by air mass origin, whereas effects of particle NC were not modified.

Conclusions

Results show an elevated risk of cardiovascular mortality in Beijing from short-term exposure to particulate air pollution in the sub-micrometer range. Results also indicate that locally produced smaller particles and regionally transported particles may exhibit different effects in Beijing.     

MA‐NOTMP: A Triazacyclononane Trimethylphosphinate Based Bifunctional Chelator for Gallium Radiolabelling of Biomolecules

In the past few years, gallium‐68 has demonstrated significant potential as a radioisotope for positron emission tomography (PET), and the optimization of chelators for gallium coordination is a major goal in the development of radiopharmaceuticals. Methylaminotriazacyclononane trimethylphosphinate (MA‐NOTMP), a new C‐functionalized triazacyclononane derivative with phosphinate pendant arms, presents excellent coordination properties for ⁶⁸Ga (low ligand concentration, labelling at low pH even at room temperature). A “ready‐to‐be‐grafted” bifunctional chelating agent (p‐NCS‐Bz‐MA‐NOTMP) was prepared to allow ⁶⁸Ga labelling of sensitive biological vectors. Conjugation to a bombesin_(7–14) derivative was performed, and preliminary in vitro experiments demonstrated the potential of MA‐NOTMP in the development of radiopharmaceuticals. This new chelator is therefore of major interest for labelling sensitive biomolecules, and further in vivo experiments will soon be performed.     

An X‐FEM‐based numerical–asymptotic expansion for simulating a Stokes flow near a sharp corner

A numerical technique that is based on the integration of the asymptotic solution in the numerical framework for computing the local singular behavior of Stokes flow near a sharp corner is presented. Moffat's asymptotic solution is used, and special enriched shape functions are developed and integrated in the extended finite element method (X‐FEM) framework to solve the Navier–Stokes equations. The no‐slip boundary condition on the walls of the corner is enforced via the use of Lagrange multipliers. Flows around corners with different angles are simulated, and the results are compared with both those of the known analytic solution and the X‐FEM with no special enrichment near the corner. The results of the present technique are shown to greatly reduce the error made in computing the pressure and velocity fields near a corner tip without the need for mesh refinement near the corner. The method is then applied to the estimation of the permeability of a network of fibers, where it is shown that the local small‐scale pressure singularities have a large impact on the large‐scale network permeability. Copyright © 2014 John Wiley & Sons, Ltd.