X-ray Linear Dichroic Tomography of Crystallographic and Topological Defects

The functionality of materials is determined by their composition and microstructure, that is, the distribution and orientation of crystalline grains, grain boundaries and the defects within them. The characterisation of the material's microstructure is therefore critical for materials applications such as catalysis, energy storage and buildings. Until now, characterization techniques that map the distribution of grains, their orientation, and the presence of defects have either been limited to surface investigations, to spatial resolutions of a few hundred nanometres, or to systems of thickness around one hundred nanometres, thus requiring destructive sample preparation for measurements and preventing the study of system-representative volumes or the investigation of materials under operational conditions. Here, we present X-ray linear dichroic orientation tomography, a quantitative, non-invasive technique that allows for an intra- and inter-granular characterisation of extended polycrystalline and amorphous materials in three dimensions (3D). We present the detailed characterisation of a polycrystalline sample of vanadium pentoxide (V2O5), a key catalyst in the production of sulfuric acid. In addition to determining the nanoscale composition, we map the crystal orientation throughout the polycrystalline sample with 73 nm spatial resolution. We identify grains, as well as twist, tilt, and twin grain boundaries. We further observe the creation and annihilation of topological defects promoted by the presence of volume crystallographic defects in 3D. Our method's non-destructive and spectroscopic nature opens the door to in-operando combined chemical and microstructural investigations of functional materials, including energy and mechanical materials in existing industries, as well as quantum materials for future technologies

From preclinical development to clinical application : kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial

Introduction A variety of radiolabelled minigastrin analogues targeting the cholecystokinin 2 (CCK2) receptor were developed and compared in a concerted preclinical testing to select the most promising radiotracer for diagnosis and treatment of medullary thyroid carcinoma (MTC). DOTA-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (CP04) after labelling with 111In displayed excellent characteristics, such as high stability, receptor affinity, specific and persistent tumour uptake and low kidney retention in animal models. Therefore, it was selected for further clinical evaluation within the ERA-NET project GRAN-T-MTC. Here we report on the development of a pharmaceutical freeze-dried formulation of the precursor CP04 for a first multi-centre clinical trial with 111In-CP04 in MTC patients. Materials and methods The kit formulation was optimised by adjustment of buffer, additives and radiolabelling conditions. Three clinical grade batches of a final kit formulation with two different amounts of peptide (10 or 50 μg) were prepared and radiolabelled with 111In. Quality control and stability assays of both the kits and the resulting radiolabelled compound were performed by HPLC analysis. Results Use of ascorbic acid buffer (pH 4.5) allowed freeze-drying of the kit formulation with satisfactory pellet-formation. Addition of methionine and gentisic acid as well as careful selection of radiolabelling temperature was required to avoid extensive oxidation of the Met11-residue. Trace metal contamination, in particular Zn, was found to be a major challenge during the pharmaceutical filling process in particular for the 10 μg formulation. The final formulations contained 10 or 50 μg CP04, 25 mg ascorbic acid, 0.5 mg gentisic acid and 5 mg l-methionine. The radiolabelling performed by incubation of 200-250 MBq 111InCl3 at 90°C for 15 min resulted in reproducible radiochemical purity (RCP) > 94%. Kit-stability was proven for > 6 months at + 5°C and at + 25°C. The radiolabelled product was stable for > 4 h at + 25°C. Conclusion A kit formulation to prepare 111In-CP04 for clinical application was developed, showing high stability of the kit as well as high RCP of the final product