Resonant laser ionization and mass separation of 225^{225}Ac

$^{225}$Ac is a radio-isotope that can be linked to biological vector molecules to treat certain distributed cancers using targeted alpha therapy. However, developing $^{225}$Ac-labelled radiopharmaceuticals remains a challenge due to the supply shortage of pure $^{225}$Ac itself. Several techniques to obtain pure $^{225}$Ac are being investigated, amongst which is the high-energy proton spallation of thorium or uranium combined with resonant laser ionization and mass separation. As a proof-of-principle, we perform off-line resonant ionization mass spectrometry on two samples of $^{225}$Ac, each with a known activity, in different chemical environments. We report overall operational collection efficiencies of 10.1(2)% and 9.9(8)% for the cases in which the $^{225}$Ac was deposited on a rhenium surface and a ThO$_{2}$ mimic target matrix respectively. The bottleneck of the technique was the laser ionization efficiency, which was deduced to be 15.1(6)%

Production cross-section measurements of proton-induced reactions on natural tantalum in the 0.3 GeV–1.7 GeV energy range

This work reports the production cross-section data for seventy-one radionuclides produced by 0.3 GeV–1.7 GeV protons impinging on thin tantalum targets. For that purpose, activation experiments were performed using the COSY synchrotron at FZ Jülich utilizing the stacked-foils technique and γ-ray spectrometry with high-purity germanium detectors. The Al-27(p,x)Na-24 reaction has been used as monitor reaction. All experimental data have been systematically compared with the existing literature. The excitation functions of Te-116, I-123, Dy-153 and Er-158 are reported for the first time. •Experimental data for proton-induced reactions on natural tantalum up to 1.7 GeV.•Use of the stacked-foils technique and γ-ray spectrometry.•First reported values for the production of Te-116, I-123, Dy-153 and Er-158

Production Cross-Section Measurements for Terbium Radionuclides of Medical Interest Produced in Tantalum Targets Irradiated by 0.3 to 1.7 GeV Protons and Corresponding Thick Target Yield Calculations

This work presents the production cross-sections of Ce, Tb and Dy radionuclides produced by 300 MeV to 1.7 GeV proton-induced spallation reactions in thin tantalum targets as well as the related Thick Target production Yield (TTY) values and ratios. The motivation is to optimise the production of terbium radionuclides for medical applications and to find out at which energy the purity of the collection by mass separation would be highest. For that purpose, activation experiments were performed using the COSY synchrotron at FZ Jülich utilising the stacked-foils technique and γ spectrometry with high-purity germanium detectors. The Al-27(p,x)Na-24 reaction has been used as monitor reaction. All experimental data have been systematically compared with the existing literature

Enhancement of therapeutic potential of a naturally occurring human antibody targeting a phosphorylated Ser422 containing epitope on pathological tau

Abstract Aggregation of tau protein and spreading of tau aggregates are pivotal pathological processes in a range of neurological disorders. Accumulating evidence suggests that immunotherapy targeting tau may be a viable therapeutic strategy. We have previously described the isolation of antibody CBTAU-22.1 from the memory B-cell repertoire of healthy human donors. CBTAU-22.1 was shown to specifically bind a disease-associated phosphorylated epitope in the C-terminus of tau (Ser422) and to be able to inhibit the spreading of pathological tau aggregates from P301S spinal cord lysates in vitro, albeit with limited potency. Using a combination of rational design and random mutagenesis we have derived a variant antibody with improved affinity while maintaining the specificity of the parental antibody. This affinity improved antibody showed greatly enhanced potency in a cell-based immunodepletion assay using paired helical filaments (PHFs) derived from human Alzheimer’s disease (AD) brain tissue. Moreover, the affinity improved antibody limits the in vitro aggregation propensity of full length tau species specifically phosphorylated at position 422 produced by employing a native chemical ligation approach. Together, these results indicate that in addition to being able to inhibit the spreading of pathological tau aggregates, the matured antibody can potentially also interfere with the nucleation of tau which is believed to be the first step of the pathogenic process. Finally, the functionality in a P301L transgenic mice co-injection model highlights the therapeutic potential of human antibody dmCBTAU-22.1