Combining X-ray data on thioflavin-T and theoretical calculations on its binding to a peptide model for Aβ_{1 –42} fibrils gives evidence of main stabilizing interactions, which influence the dihedral angle between the two moieties of thioflavin-T and thereby its fluorescence properties; these results shed new light on possible strategies for the design of dyes to bind amyloid fibrils more specifically.

Long-circulating, transfection-competent lipid nanoparticle (LNP)-mRNA delivery systems are critical for achieving efficient transfection in extrahepatic tissues. Here we investigate the properties of LNP mRNA systems containing high proportions of bilayer forming lipids, using equimolar egg sphingomyelin and cholesterol as the bilayer-forming components. We show that LNP mRNA systems prepared at bilayer lipid to ionizable lipid molar ratios of 4-0.67 exhibit high mRNA encapsulation efficiencies (90–100%) and excellent transfection potencies in vitro. Systems with bilayer lipid to ionizable lipid molar ratios equating to 4 exhibit a liposomal morphology with a solid core suspended in an aqueous interior surrounded by a lipid bilayer. These liposomal LNPs exhibit longer circulation lifetimes than LNP systems with Onpattro-like lipid compositions and have enhanced extrahepatic transfection properties. The prolonged blood circulation lifetime is attributed to reduced plasma protein adsorption. The transfection competency of liposomal LNP systems is attributed to export of the solid core containing mRNA from the LNP as the endosomal pH is lowered.

Effective use of the 225 A c decay chain in targeted internal radioimmunotherapy requires the retention of both 225 A c and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the 225 A c decay chain: 221 F r (218 keV) and 213 B i (440 keV). Image quality phantoms were used to assess the performance of two collimators for simultaneous 221 F r and 213 B i imaging in terms of contrast and noise. A hotrod resolution phantom containing clusters of thin rods with diameters ranging between 0.85 and 1.70 mm was used to assess resolution. To demonstrate ability to simultaneously image dynamic 221 F r and 213 B i activity distributions, a phantom containing a 213 B i generator from 225 A c was imaged. These tests were performed with two collimators, a high-energy ultra-high resolution (HEUHR) collimator and an ultra-high sensitivity (UHS) collimator. Values consistent with activity concentrations determined independently via gamma spectroscopy were observed in high activity regions of the images. In hotrod phantom images, the HEUHR collimator resolved all rods for both 221 F r and 213 B i images. With the UHS collimator, no rods were resolvable in 213 B i images and only rods ⩾1.3 mm were resolved in 221 F r images. After eluting the 213 B i generator, images accurately visualized the reestablishment of transient equilibrium of the 225 A c decay chain. The feasibility of evaluating the pharmacokinetics of the 225 A c decay chain in vivo has been demonstrated. This presented method requires the use of a high-performance high-energy collimator.