Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications

We report the first targeted nuclear medicine application of the lanthanum radionuclides ^132/135La. These isotopes represent a matched pair for diagnosis via the positron emissions of ¹³²La and therapy mediated by the Auger electron emissions of ¹³⁵La. We identify two effective chelators, known as DO3Apic and macropa, for these radionuclides. The 18-membered macrocycle, macropa, bound ^132/135La with better molar activity than DO3Apic under similar conditions. These chelators were conjugated to the prostate-specific membrane antigen (PSMA)-targeting agent DUPA to assess the use of radiolanthanum for in vivo imaging. The ^132/135La-labeled targeted constructs showed high uptake in tumor xenografts expressing PSMA. This study validates the use of these radioactive lanthanum isotopes for imaging applications and motivates future work to assess the therapeutic effects of the Auger electron emissions of ¹³⁵La.     

Light-Activated Protein Conjugation and 89Zr-Radiolabelling with Water-Soluble Desferrioxamine Derivatives

Protein-conjugates are vital tools in biomedical research, drug discovery and imaging science. For example, functionalised monoclonal antibodies (mAbs) coupled to the desferrioxamine B (DFO) chelate and radiolabelled with ⁸⁹Zr⁴⁺ ions are used as radiopharmaceuticals for diagnostic positron emission tomography (PET). In this context, protein functionalisation requires the formation of a covalent bond that must be achieved without compromising the biological properties of the mAb. Photochemistry offers new synthetic routes toward protein conjugates like ⁸⁹Zr-mAbs but to harness the potential of light-induced conjugation reactions new photoactivatable reagents are required. Herein, we introduce two photoactivatable DFO-derivatives functionalised with an aryl azide (ArN₃) for use in light-activated conjugation and radiosynthesis of ⁸⁹Zr-mAbs. Incorporation of a tris-polyethylene glycol (PEG)₃ linker between DFO and the ArN₃ group furnished water-soluble chelates that were used in the one-pot, photoradiosynthesis of different ⁸⁹Zr-radiolabelled protein conjugates with radiochemical yields up to 72.9±1.9 %. Notably, the DFO-PEG₃ chelates can be readily synthesised in accordance with Good Laboratory Practice (GLP), which will facilitate clinical trials with photoradiolabelled ⁸⁹Zr-mAbs.     

Real-Time Reconstruction of Arbitrary Slices for Quantitative and In Situ 3D Characterization of Nanoparticles

A detailed 3D investigation of nanoparticles at a local scale is of great importance to connect their structure and composition to their properties. Electron tomography has therefore become an important tool for the 3D characterization of nanomaterials. 3D investigations typically comprise multiple steps, including acquisition, reconstruction, and analysis/quantification. Usually, the latter two steps are performed offline, at a dedicated workstation. This sequential workflow prevents on-the-fly control of experimental parameters to improve the quality of the 3D reconstruction, to select a relevant nanoparticle for further characterization, or to steer an in situ tomography experiment. Here, an efficient approach to overcome these limitations is presented, based on the real-time reconstruction of arbitrary 2D reconstructed slices through a 3D object. Implementation of this method may lead to generalized implementation of electron tomography for routine nanoparticle characterization in 3D.     

A Macroscopically Relevant 3D‐Metrology Approach for Nanocatalysis Research

A 3D nanometrological approach, which considers as an unbiased validation criterion the quantitative match between values of properties determined by macroscopic characterization techniques and those determined from the nanoscopic results, is developed to unveil the details of complex nanocatalysts. This approach takes into account both the peculiar characteristics of this type of materials and the large influence of noise in the tilt series. It combines, in an optimized way, the latest experimental developments in high angle annular dark field scanning transmission electron microscopy mode (HAADF‐STEM) tomography, such as batch tomography, image denoising by undecimated wavelet transforms, improved reconstructions by total variation minimization and a more efficient, user‐independent, segmentation scheme. To illustrate the use of this novel approach, the 3D structural characterization of a model nanocatalyst comprising gold nanoparticles dispersed on the surface of CeO₂ nanocubes is performed, and the obtained results used to compute the values of different macroscopic chemical and textural properties. Comparison with values obtained by macroscopic characterization techniques match very closely those obtained by 3D nanometrology. Importantly, the new approach described in this work also illustrates a pipeline for nearly fully automated HAADF‐STEM tomography studies, guaranteeing reliable correlations between nanoscopic and macroscopic properties.     

Nanojunction‐Mediated Photocatalytic Enhancement in Heterostructured CdS/ZnO,CdSe/ZnO,and CdTe/ZnO Nanocrystals

A series of highly efficient semiconductor nanocrystal (NC) photocatalysts have been synthesized by growing wurtzite‐ZnO tetrahedrons around pre‐formed CdS, CdSe, and CdTe quantum dots (QDs). The resulting contact between two small but high‐quality crystals creates novel CdX/ZnO heterostructured semiconductor nanocrystals (HSNCs) with extensive type‐II nanojunctions that exhibit more efficient photocatalytic decomposition of aqueous organic molecules under UV irradiation. Catalytic testing and characterization indicate that catalytic activity increases as a result of a combination of both the intrinsic chemistry of the chalcogenide anions and the heterojunction structure. Atomic probe tomography (APT) is employed for the first time to probe the spatial characteristics of the nanojunction between cadmium chalcogenide and ZnO crystalline phases, which reveals various degrees of ion exchange between the two crystals to relax large lattice mismatches. In the most extreme case, total encapsulation of CdTe by ZnO as a result of interfacial alloying is observed, with the expected advantage of facilitating hole transport for enhanced exciton separation during catalysis.     

Design,development and first experiments on the X‐ray imaging beamline at Indus‐2 synchrotron source RRCAT,India

A full‐field hard X‐ray imaging beamline (BL‐4) was designed, developed, installed and commissioned recently at the Indus‐2 synchrotron radiation source at RRCAT, Indore, India. The bending‐magnet beamline is operated in monochromatic and white beam mode. A variety of imaging techniques are implemented such as high‐resolution radiography, propagation‐ and analyzer‐based phase contrast imaging, real‐time imaging, absorption and phase contrast tomography etc. First experiments on propagation‐based phase contrast imaging and micro‐tomography are reported.     

Three-dimensional characterization of fatigue-relevant intermetallic particles in high-strength aluminium alloys using synchrotron X-ray nanotomography

Second-phase particles and small porosities are known to favour fatigue crack initiation in high-strength aluminium alloys 2050-T8 and 7050-T7451. Using high-resolution X-ray tomography (320 nm voxel size), with Paganin reconstruction algorithms, the probability that large clusters of particles contain porosities could be measured for the first time in 3D, as well as precise 3D size distributions. Additional holotomography imaging provided improved spatial resolution (50 nm voxel size), allowing to estimate the probability of finding cracked particles in the as-received material state. The extremely precise 3D shape (including cracks) as well as local chemistry of the particles has been determined. This experiment enabled unprecedented 3D identification of detrimental stress risers relevant for fatigue in as-received aluminium alloys.     

Nonequilibrium Effects During Spontaneous Imbibition

Accurate models of multiphase flow in porous media and predictions of oil recovery require a thorough understanding of the physics of fluid flow. Current simulators assume, generally, that local capillary equilibrium is reached instantaneously during any flow mode. Consequently, capillary pressure and relative permeability curves are functions solely of water saturation. In the case of imbibition, the assumption of instantaneous local capillary equilibrium allows the balance equations to be cast in the form of a self-similar, diffusion-like problem. Li et al. [J. Petrol. Sci. Eng. 39(3) (2003), 309–326] analyzed oil production data from spontaneous countercurrent imbibition experiments and inferred that they observed the self-similar behavior expected from the mathematical equations. Others (Barenblatt et al. [Soc. Petrol. Eng. J. 8(4) (2002), 409–416]; Silin and Patzek [Transport in Porous Media 54 (2004), 297–322]) assert that local equilibirum is not reached in porous media during spontaneous imbibition and nonequilibirium effects should be taken into account. Simulations and definitive experiments are conducted at core scale in this work to reveal unequivocally nonequilbirium effects. Experimental in-situ saturation data obtained with a computerized tomography scanner illustrate significant deviation from the numerical local-equilibrium based results. The data indicates: (i) capillary imbibition is an inherently nonequilibrium process and (ii) the traditional, multi-phase, reservoir simulation equations may not well represent the true physics of the process.     

Pseudo-schlieren CT measurement of three-dimensional flow phenomena on shock waves and vortices discharged from open ends

1A pseudo-schlieren technique is applied to the interferometric computed tomography (CT) measurement of three-dimensional (3-D) shock waves discharged from a square open end and a pair of circular open ends in a shock tube experiment. The experiment is performed for incident shock Mach numbers of 2.0 and 2.2 in nitrogen gas under supersonic post shock flow conditions at the open end. The 3-D density-gradient distributions are evaluated from the CT data of the 3-D density distributions, and are depicted in gray-scale CT images of the gradient magnitude and in pseudo-color CT images of the gradient component. The resultant pseudo-schlieren CT images clearly illustrate the 3-D flow features of shock waves, contact surfaces, and the other sharp density fronts. Their image characteristics and meaning in gas dynamics are discussed in comparison with the pseudo-color images of the density. We demonstrate that the pseudo-schlieren CT technique is a useful tool for studying 3-D problems in shock dynamics. Communicated by K. Takayama PACS 47.32.cd; 47.40.Nm; 47.80.jk