Dose integration and dose rate characteristics of a NiPAM polymer gel MRI dosimeter system

The normoxic polymer gel dosimeter based on N-isopropyl acrylamide (NiPAM) is a promising full 3D-dosimeter with high spatial resolution and near tissue equivalency. NiPAM gel samples were irradiated to different doses using a linear accelerator. The absorbed dose was evaluated using MRI and statistical significance of the analysed data was calculated. The analysis was carried out using an in-house developed software. It was found that the gel dosimeter responded linearly to the absorbed dose. The gel exhibited a dose rate dependence, as well as a dependence on the sequential beam irradiation scheme. A higher dose rate, as well as a higher dose per sequential beam, resulted in a lower dose response

Ligand-Directed Functional Selectivity at the Mu Opioid Receptor Revealed by Label-Free Integrative Pharmacology On-Target

Development of new opioid drugs that provide analgesia without producing dependence is important for pain treatment. Opioid agonist drugs exert their analgesia effects primarily by acting at the mu opioid receptor (MOR) sites. High-resolution differentiation of opioid ligands is crucial for the development of new lead drug candidates with better tolerance profiles. Here, we use a label-free integrative pharmacology on-target (iPOT) approach to characterize the functional selectivity of a library of known opioid ligands for the MOR. This approach is based on the ability to detect dynamic mass redistribution (DMR) arising from the activation of the MOR in living cells. DMR assays were performed in HEK-MOR cells with and without preconditioning with probe molecules using label-free resonant waveguide grating biosensors, wherein the probe molecules were used to modify the activity of specific signaling proteins downstream the MOR. DMR signals obtained were then translated into high resolution heat maps using similarity analysis based on a numerical matrix of DMR parameters. Our data indicate that the iPOT approach clearly differentiates functional selectivity for distinct MOR signaling pathways among different opioid ligands, thus opening new avenues to discover and quantify the functional selectivity of currently used and novel opioid receptor drugs