Non-specific irreversible Zr-mAb uptake in tumours: evidence from biopsy-proven target-negative tumours using Zr-immuno-PET.

Background: Distribution of mAbs into tumour tissue may occur via different processes contributing differently to the Zr-mAb uptake on PET. Target-specific binding in tumours is of main interest; however, non-specific irreversible uptake may also be present, which influences quantification. The aim was to investigate the presence of non-specific irreversible uptake in tumour tissue using Patlak linearization on Zr-immuno-PET data of biopsy-proven target-negative tumours.

How to obtain the image-derived blood concentration from Zr-immuno-PET scans.

Background: PET scans using zirconium-89 labelled monoclonal antibodies (Zr-mAbs), known as Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling.

Zr-Immuno-PET with Immune Checkpoint Inhibitors: Measuring Target Engagement in Healthy Organs.

Introduction: Zr-immuno-PET (positron emission tomography with zirconium-89-labeled monoclonal antibodies ([Zr]Zr-mAbs)) can be used to study the biodistribution of mAbs targeting the immune system. The measured uptake consists of target-specific and non-specific components, and it can be influenced by plasma availability of the tracer. To find evidence for target-specific uptake, i.

Validation of simplified uptake measures against dynamic Patlak K for quantification of lesional Zr-Immuno-PET antibody uptake.

Purpose: Positron emission tomography imaging of zirconium-89-labelled monoclonal antibodies (Zr-Immuno-PET) allows for visualisation and quantification of antibody uptake in tumours in vivo. Patlak linearization provides distribution volume (V) and nett influx rate (K) values, representing reversible and irreversible uptake, respectively. Standardised uptake value (SUV) and tumour-to-plasma/tumour-to-blood ratio (TPR/TBR) are often used, but their validity depends on the comparability of plasma kinetics and clearances.

Optimal imaging time points considering accuracy and precision of Patlak linearization for Zr-immuno-PET: a simulation study.

Purpose: Zirconium-89-immuno-positron emission tomography (Zr-immuno-PET) has enabled visualization of zirconium-89 labelled monoclonal antibody (Zr-mAb) uptake in organs and tumors in vivo. Patlak linearization of Zr-immuno-PET quantification data allows for separation of reversible and irreversible uptake, by combining multiple blood samples and PET images at different days. As one can obtain only a limited number of blood samples and scans per patient, choosing the optimal time points is important.

Transcranial Direct Current Stimulation Targeting the Entire Motor Network Does Not Increase Corticospinal Excitability.

Transcranial direct current stimulation (tDCS) over the contralateral primary motor cortex of the target muscle (conventional tDCS) has been described to enhance corticospinal excitability, as measured with transcranial magnetic stimulation. Recently, tDCS targeting the brain regions functionally connected to the contralateral primary motor cortex (motor network tDCS) was reported to enhance corticospinal excitability more than conventional tDCS. We compared the effects of motor network tDCS, 2 mA conventional tDCS, and sham tDCS on corticospinal excitability in 21 healthy participants in a randomized, single-blind within-subject study design.

The Two-Component System ChtRS Contributes to Chlorhexidine Tolerance in Enterococcus faecium.

is one of the primary causes of nosocomial infections. Disinfectants are commonly used to prevent infections with multidrug-resistant in hospitals. Worryingly, strains that exhibit tolerance to disinfectants have already been described.

Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host.

T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment.