Optimizing 211At production cross section by studying the rise of 210At cross section: First measurement using Linac SPIRAL2.

BACKGROUND: Only a small fraction of patients with colorectal liver metastases (CLM) is eligible for curative resection, and novel treatment options are highly needed. The high linear-energy transfer of short-ranged alpha particles can induce complex double-stranded DNA breaks, leading to cell death. With no known resistance mechanism, alpha-particle emitting isotopes represent a promising tool in cancer management. In targeted alpha therapy (TAT), an alpha-particle emitting isotope is attached to a tumor-targeting antibody (hereafter TAT antibody), ensuring specific delivery to the tumor. By substituting the alpha-particle emitting isotope (Actinium-225, 225Ac) with a diagnostic isotope (Zirconium-89, 89Zr), the in-vivo distribution of the TAT antibody can be monitored using PET/SPECT/CT. The aim of this work was to set up robust labeling and PET/SPECT protocols to evaluate TAT in CLM using novel experimental models. METHODS: For SPECT-imaging of 225Ac daughter isotopes, the combined gamma emission spectra were gated at 218 keV ± 20% and 440 keV ± 20% for Francium-221 and Bismuth-213, respectively. 89Zr was labeled to a desferrioxamine* (DFO*) conjugated TAT antibody, which recognizes both the murine and human antigen. Indium-111 (111In) labeling was performed through diethylenetriaminepentaacetic acid (DTPA) conjugated to an isotype antibody. Radiochemical purity and protein integrity were assessed by size exclusion HPLC, iTLC and SDS-PAGE. For orthotopic CLM model development, 106 cells of human colorectal cancer cell lines HT-55 or LS1034 were injected in the spleen of female Rj:NMRI-Foxn1nu mice, followed by splenectomy. Tumor growth was monitored by T2-weighted MR-imaging. Non-tumor bearing mice (n = 12, 3 per group) were injected with 4 MBq of 10, 20, 50 or 100 µg 89Zr-TAT antibody to evaluate biodistribution and the mice scanned on day 2, 4 and 6 after iv injection. RESULTS: Francium-221 and Bismuth-213 could be separately visualized after free Actinium-225 administration (i.v.). 89Zr and 111In were routinely labeled to their respective antibody with up to 500 MBq/mg with >95% radiochemical purity. 89Zr-DFO*-TAT antibody showed >95% radiochemical purity and >95% protein integrity after 7 days stability test in serum, shown by iTLC and SDS-PAGE. SPECT/CT of 89Zr-DFO*-TAT antibody in non-tumor bearing mice showed little uptake in healthy tissues apart from the liver due to hepatic antibody clearance. Orthotopic models of CLM show reproducible development of metastases for HT-55 and LS1034 within 3 weeks. CONCLUSION: Robust labeling methods, PET/SPECT imaging protocols and suitable animal models of CLM were established. Results of our dual-isotope SPECT/CT imaging of our 89Zr-DFO*-TAT antibody in comparison with an 111In-labeled isotype antibody, together with efficacy data of the TAT, will be presented at the meeting. Citation Format: Frans V. Suurs, Alexander Kristian, Gebregziabher Petros, Yuan Zeng Feng, Karianne G. Fleten, Roger M. Bjerke, Alan Cuthbertson, Kjersti Flatmark. SPECT-imaging guided development and evaluation of targeted alpha therapy (TAT) for colorectal liver metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2467.

This review provides a general overview of the current achievements and challenges in translational dosimetry for targeted alpha therapy (TAT). The concept of targeted radionuclide therapy (TRNT) is described with an overview of its clinical applicability and the added value of TAT is discussed. For TAT, we focused on actinium-225 (225Ac) as an example for alpha particle emitting radionuclides and their features, such as limited range within tissue and high linear energy transfer, which make alpha particle emissions more effective in targeted killing of tumour cells compared to beta radiation. Starting with the state-of-the-art dosimetry for TRNT and TAT, we then describe the challenges that still need to be met in order to move to a personalized dosimetry approach for TAT. Specifically for 225Ac, we discuss the recoiled daughter effect which may provoke significant damage to healthy tissue or organs and should be considered. Next, a broad overview is given of the pre-clinical research on 225Ac-TAT with an extensive description of tools which are only available in a pre-clinical setting and their added value. In addition, we review the preclinical biodistribution and dosimetry studies that have been performed on TAT-agents and more specifically of 225Ac and its multiple progeny, and describe their potential role to better characterize the pharmacokinetic (PK) profile of TAT-agents and to optimize the use of theranostic approaches for dosimetry. Finally, we discuss the support pre-clinical studies may provide in understanding dose-effect relationships, linking radiation dose quantities to biological endpoints and even moving away from macro- to microdosimetry. As such, the translation of pre-clinical findings may provide valuable information and new approaches for improved clinical dosimetry, thus paving the way to personalized TAT.

Radionuclide Therapy (RNT) and Radioimmunotherapy (RIT) are potentially of great interest for cancer therapy. In many therapeutic applications alpha emitters should be much more effective than already-approved beta emitters due to the short range and high linear energy transfer of alpha particles. 213Bi is an important alpha emitter already used in clinical trials but the half-life of this radioisotope is short (46 minutes) and so its use is limited for certain therapies. 211At is potentially very interesting for medical purposes because of its longer half-life of 7.2 hours, and suitable decay scheme. We have studied the cyclotron-based production of 211At via the reaction 209Bi(α, 2n), this production route probably being the most promising in the long term. The energy dependence of thick target yields and the reaction cross sections for the production of 211At and 210At were determined and found to be in good agreement with literature. The best energy to produce 211At is 28-29 MeV. The possible production of the undesired, highly radiotoxic, and long-lived alpha-emitting 210Po (138.38 days), which is produced from decay of 210At, is also discussed.

Cross section measurements of deuteron induced nuclear reactions on natural titanium up to 34 MeV

39IN - The next generation of radioimmunotherapy: Targeted alpha therapy (TAT)

IAEA activities to support the member states in the production of targeted alpha therapy radiopharmaceuticals.

The interest in 209Bi, the only stable isotope of this element, originates from its proposed use in the spallation module and as moderator/coolant of an accelerator driven system (ADS). Inelastic scattering that constitutes 30% of the total neutron cross section of 209Bi is a major contributor to uncertainties in predicted ADS parameters. New data were obtained for production cross sections of 19 transitions up to about 18 MeV, incident energy. One transition was observed per excited level for the first 8 levels. From the measured gamma‐ray production cross sections, total and level inelastic cross sections were deduced. The experiment was performed at GELINA, with a white neutron spectrum, at 200 m flight path length using the time‐of‐flight method. The gamma rays from the 209Bi(n,n′γ)209Bi reaction were detected with two large volume HPGe detectors and the neutron flux was monitored with a multilayer 235U fission chamber. For the main transitions the inelastic cross section is given with an incident neutron energy resolution ranging from 1.1 keV at 1 MeV to 35.7 keV at 10 MeV within overall statistical error of less than 5%.

Infinite-order sudden approximation (IOSA) calculations of the phenomenological production and relaxation cross sections governing the magnetoviscosity effect have been undertaken for the system N2 at infinite dilution in He for the purpose of testing the usefulness of the IOSA procedure. Three l-labeling schemes (IL, FL, and AVL) have been employed and the results obtained for each of the three types of cross sections occuring in the viscomagnetic effect have been compared. For the relaxation cross sections σT( j′j‖Ek), σ(1)η( j′j‖Ek), and σ(2)η( j′j‖Ek), the IL/FL and AVL results differ by less than 5% on the average, but for the production cross sections σTη( j′j‖Ek), the three schemes IL, FL, AVL give widely differing results (one order of magnitude and sign). Thermally averaged phenomenological cross sections at 77.5 K were obtained for three potentials of the MSV type: one obtained from beam experiments and two using the beam scattering isotropic part and modified anisotropy parameters. For one of the modified anisotropic potentials giving reasonable agreement of the cross section σT calculated using the IOSA procedure and obtained from experiment, initial close-coupled calculations were performed at a kinetic energy of 54 cm−1. The IOSA AVL procedure gave results for j, j′ = 1, 3 differing by as much as 30% for σT( j′j‖Ek), and σ(κ)η( j′j‖Ek) and by as much as a factor of 2 for σTη( j′j‖Ek). Tentatively, it appears that in order to calculate production cross sections with reasonable confidence and accuracy, it will be necessary either to modify the CSA and IOSA methods or to use the more accurate CC procedure.

Cross section measurements were made of prompt gamma‐ray production as a function of neutron energy using the germanium array for neutron induced excitations (GEANIE) at LANSCE. Measuring the prompt reaction gamma rays as a function of incident neutron energy provides more precise understanding of the spins populated by the pre‐equilibrium reaction. The effect of the spin distribution in pre‐equilibrium reactions has been investigated using the GNASH reaction code. Widely used classical theories such as the exciton model usually assume that the spin distribution of the pre‐equilibrium reaction is the same as the spin distribution of the compound nucleus reaction mechanism. In the present approach, the pre‐equilibrium reaction spin distribution was calculated using the quantum mechanical theory of Feshbach, Kerman, and Koonin (FKK). This pre‐equilibrium spin distribution was incorporated into the GNASH code and the gamma‐ray production cross sections were calculated and compared with experimental data. Spin distributions peak at lower spin when calculated with the FKK formulation than with the Compound Nuclear theory. The measured partial gamma‐ray cross sections reflect this spin difference. Realistic treatment of the spin distribution improves the accuracy of calculations of gamma‐ray production cross sections.

The STAYSL PNNL computer code, a descendant of the STAY'SL code [1], performs neutron spectral adjustment of a starting neutron spectrum, applying a least squares method to determine adjustments based on saturated activation rates, neutron cross sections from evaluated nuclear data libraries, and all associated covariances. STAYSL PNNL is provided as part of a comprehensive suite of programs [2], where additional tools in the suite are used for assembling a set of nuclear data libraries and determining all required corrections to the measured data to determine saturated activation rates. Neutron cross section and covariance data are taken from the International Reactor Dosimetry File (IRDF-2002) [3], which was sponsored by the International Atomic Energy Agency (IAEA), though work is planned to update to data from the IAEA's International Reactor Dosimetry and Fusion File (IRDFF) [4]. The nuclear data and associated covariances are extracted from IRDF-2002 using the third-party NJOY99 computer code [5]. The NJpp translation code converts the extracted data into a library data array format suitable for use as input to STAYSL PNNL. The software suite also includes three utilities to calculate corrections to measured activation rates. Neutron self-shielding corrections are calculated as a function of neutron energy with the SHIELD code and are applied to the group cross sections prior to spectral adjustment, thus making the corrections independent of the neutron spectrum. The SigPhi Calculator is a Microsoft Excel spreadsheet used for calculating saturated activation rates from raw gamma activities by applying corrections for gamma self-absorption, neutron burn-up, and the irradiation history. Gamma self-absorption and neutron burn-up corrections are calculated (iteratively in the case of the burn-up) within the SigPhi Calculator spreadsheet. The irradiation history corrections are calculated using the BCF computer code and are inserted into the SigPhi Calculator workbook for use in correcting the measured activities. Output from the SigPhi Calculator is automatically produced, and consists of a portion of the STAYSL PNNL input file data that is required to run the spectral adjustment calculations. Within STAYSL PNNL, the least-squares process is performed in one step, without iteration, and provides rapid results on PC platforms. STAYSL PNNL creates multiple output files with tabulated results, data suitable for plotting, and data formatted for use in subsequent radiation damage calculations using the SPECTER computer code (which is not included in the STAYSL PNNL suite). All components of the software suite have undergone extensive testing and validation prior to release and test cases are provided with the package.

The explicit expressions for calculating the in-medium $N+N\ensuremath{\rightarrow}\ensuremath{\Delta}+\ensuremath{\Delta}$ and $\ensuremath{\Delta}+\ensuremath{\Delta}\ensuremath{\rightarrow}N+N$ cross section have been derived within the framework of the self-consistent relativistic Boltzmann-Uehling-Uhlenbeck approach in which the deltas and nucleons are treated on an equal footing. The obtained cross sections are consistent with the other integrands of the transport model. The theoretical prediction of the free double-$\ensuremath{\Delta}$ production cross section is in good agreement with the experimental data. All the medium effects on the double-$\ensuremath{\Delta}$ production and absorption cross section are studied systematically, and strong medium corrections are found. Our numerical results show that it would be important to take the $N+N\ensuremath{\rightarrow}\ensuremath{\Delta}+\ensuremath{\Delta}$ and $\ensuremath{\Delta}+\ensuremath{\Delta}\ensuremath{\rightarrow}N+N$ channel into account in the study of relativistic heavy-ion collisions at intermediate and high energies.

Since the discovery of the top quark in 1995 at the Fermilab Tevatron collider, the ttbar production cross section has been measured with ever higher precision. Up to now, no deviation from the standard model has been found. With the restart of the LHC mid of this year, the LHC enables us to measure ttbar production at the previously unreached energy of 13 TeV. In this report, the very first ttbar cross section measurement in the dileptonic channel using the electron-muon final state is described. Systematic uncertainties are discussed and the measurement is compared to theory predictions. Presented at TOP2015 8th International Workshop on Top Quark Physics Measurement of the top quark pair production cross section at 13 TeV with the CMS detector Till Arndt∗† Deutsches Elektronen-Synchrotron Hamburg and Zeuthen (DE) E-mail: till.michael.arndt@cern.ch Since the discovery of the top quark in 1995 at the Fermilab Tevatron collider, the ttbar production cross section has been measured with ever higher precision. By now, no deviation from the standard model has been found. With the restart of the LHC mid of this year, the LHC enables us to measure ttbar production at a previously unreached energy of 13 TeV. In this presentation, the very first ttbar cross section measurement from CMS using the electron-muon final state is discussed. Moreover, detector related efficiencies are outlined and the measurement is compared to theory predictions. 8th International Workshop on Top Quark Physics, TOP2015 14-18 September, 2015 Ischia, Italy ∗Speaker. †A footnote may follow. c © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). http://pos.sissa.it/ Measurement of the top quark pair production cross section at 13 TeV with the CMS detector Till Arndt

The cosmic-ray flux of antiprotons is measured with high precision by the space-borne particle spectrometers AMS-02.Its interpretation requires a correct description of the dominant production process for antiprotons in our Galaxy, namely, the interaction of cosmic-ray proton and helium with the interstellar medium. In the light of new cross section measurements by the NA61 experiment of $p + p \rightarrow \bar{p} + X$ and the first ever measurement of $p + \mathrm{He} \rightarrow \bar{p} + X$ by the LHCb experiment, we update the parametrization of proton-proton and proton-nucleon cross sections.We find that the LHCb $p$He data constrain a shape for the cross section at high energies and show for the first time how well the rescaling from the $pp$ channel applies to a helium target. By using $pp$, $p$He and $p$C data we estimate the uncertainty on the Lorentz invariant cross section for $p + \mathrm{He} \rightarrow \bar{p} + X$. We use these new cross sections to compute the source term for all the production channels, considering also nuclei heavier than He both in cosmic rays and the interstellar medium. The uncertainties on the total source term are at the level of $\pm20$% and slightly increase below antiproton energies of 5 GeV. This uncertainty is dominated by the $p+p \rightarrow \bar{p} + X$ cross section, which translates into all channels since we derive them using the $pp$ cross sections. The cross sections to calculate the source spectra from all relevant cosmic-ray isotopes are provided in the Supplemental Material. We finally quantify the necessity of new data on antiproton production cross sections, and pin down the kinematic parameter space which should be covered by future data.

The injection of energetic neutral particles into the plasma of magnetic confinement fusion reactors is a widely-accepted method for heating such plasmas; various types of neutral beam are also used for diagnostic purposes. Accurate atomic data are required to properly model beam penetration into the plasma and to interpret photoemission spectra from both the beam particles themselves (e.g. beam emission spectroscopy) and from plasma impurities with which they interact (e.g. charge exchange recombination spectroscopy). This paper reviews and compares theoretical methods for calculating ionization, excitation and charge exchange cross sections applied to several important processes relevant to neutral hydrogen beams, including H + Be4+ and H + H+. In particular, a new cross section for the proton-impact ionization of H (1s) is recommended which is significantly larger than that previously accepted at fusion-relevant energies. Coefficients for an empirical fit function to this cross section and to that of the first excited states of H are provided and uncertainties estimated. The propagation of uncertainties in this cross section in modeling codes under JET-like conditions has been studied and the newly-recommended values determined to have a significant effect on the predicted beam attenuation. In addition to accurate calculations of collisional atomic data, the use of these data in codes modeling beam penetration and photoemission for fusion-relevant plasma density and temperature profiles is discussed. In particular, the discrepancies in the modeling of impurities are reported. The present paper originates from a Coordinated Research Project (CRP) on the topic of fundamental atomic data for neutral beam modeling that the International Atomic Energy Agency (IAEA) ran from 2017 to 2022; this project brought together ten research groups in the fields of fusion plasma modeling and collisional cross section calculations. Data calculated during the CRP is summarized in an and is available online in the IAEA’s atomic database, CollisionDB.

A cross section measurement for the production of W+W- is performed. Differential measurements are reported as a function of jet multiplicity and transverse energy. The inclusive cross section is measured to be σ(p$\bar{p}$→W+W-+X=14.0±0.6(stat)$+1.2\atop{-1.0}$(syst)±0.8(lumi)±0.8(lumi) pb, consistent with the Standard Model prediction. Additionally, a search for the Higgs boson is performed in the final state of W+W- with two or more associated jets. Limits on the production cross section are set at the 95%95% confidence level, and combined with limits from related analyses. Both analyses use data collected by the CDF II detector from 9.7fb-1 of luminosity.