Separation of radium and actinium from historical Th-229 sources for production of radioisotopes for targeted alpha immunotherapy

status: publishe

Optimization of isolation and mass spectrometric analysis of lanthanides from spent nuclear fuel

status: publishe

Evaluation of the irradiation-averaged fission yield for burnup determination in spent fuel assays

In order to derive the burnup of spent nuclear fuel from the concentration of selected fission products (typically the Nd isotopes and 137Cs), their irradiation-averaged fission yields need to be known with sufficient accuracy, as they evolve with the changes in the actinide vector over the irradiation history. To obtain irradiation-averaged values, radiochemists often resort to robust generic methods – i.e., based on simple mathematical relations – that weight the fission yields according to the actinides contributing to fission, without performing core physics calculations. In order to assess the performance of those generic methods, a database of about 30 000 spent nuclear fuel inventories has been constructed from neutron transport and depletion simulations, covering a representative range of fuel enrichment, burnup, assembly designs and reactor types. When testing several existing methods for effective fission yield calculation, some inaccuracies were identified, originating from improper one-group cross-section parameters that do not accurately reflect resonance and self-shielding effects, and too crude approximations in the estimation of the actinide concentration evolution. Revised effective fission and absorption cross-section parameters are then proposed here, as a first improvement to the earlier burnup determination methods. As a second step, a novel method is proposed that reduces the error on their radiation-averaged fission yield values, and hence on burnup, while retaining a straightforward calculation scheme

Bismuth-213 labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

status: publishe

213Bismuth-labeled nanobodies as a new treatment approach in Targeted Alpha Therapy

status: publishe

Therapeutic Efficacy of Bi-213-labeled sdAbs in a Preclinical Model of Ovarian Cancer

Targeted alpha-particle therapy (TAT) might be a relevant therapeutic strategy to circumvent resistance to conventional therapies in the case of HER2-positive metastatic cancer. Single-domain antibody fragments (sdAb) are promising vehicles for TAT because of their excellent in vivo properties, high target affinity, and fast clearance kinetics. This study combines the cytotoxic α-particle emitter bismuth-213 (213Bi) and HER2-targeting sdAbs. The in vitro specificity, affinity, and cytotoxic potency of the radiolabeled complex were analyzed on HER2pos cells. Its in vivo biodistribution through serial dissections and via Cherenkov and micro-single-photon emission computed tomography (CT)/CT imaging was evaluated. Finally, the therapeutic efficacy and potential associated toxicity of [213Bi]Bi-DTPA-2Rs15d were evaluated in a HER2pos tumor model that manifests peritoneal metastasis. In vitro, [213Bi]Bi-DTPA-2Rs15d bound HER2pos cells in a HER2-specific way. In mice, high tumor uptake was reached already 15 min after injection, and extremely low uptake values were observed in normal tissues. Co-infusion of gelofusine resulted in a 2-fold reduction in kidney uptake. Administration of [213Bi]Bi-DTPA-2Rs15d alone and in combination with trastuzumab resulted in a significant increase in median survival. We describe for the very first time the successful labeling of an HER2-sdAb with the α-emitter 213Bi, and after intravenous administration, revealing high in vivo stability and specific accumulation in target tissue and resulting in an increased median survival of these mice especially in combination with trastuzumab. These results indicate the potential of [213Bi]Bi-DTPA-sdAb as a new radioconjugate for TAT, alone and as an add-on to trastuzumab for the treatment of HER2pos metastatic cancer.status: publishe