COST Action CA19114, Network for Optimized Astatine labelled Radiopharmaceuticals

Cancer is a major health concerns for European citizens. Thus, the main research aim of this Network for Optimized Astatine labeled Radiopharmaceuticals (NOAR) COST Action is to successfully demonstrate that one of the most promising radionuclides for Targeted Alpha Therapy (TAT), namely astatine-211, can become the European standard for treatment of certain cancerous pathologies. To this end, an efficient networking is essential among all European stakeholders interested in promoting astatine-211 for medical applications. NOAR COST Action brings together European and international excellence labs, astatine-211 production centers, hospitals, industry and patient associations from more than 20 countries, thus covering the whole value chain of innovation: production, chemistry, radiochemistry, biology, preclinical and clinical research and delivery of radiopharmaceuticals to patients. A European web portal will be created containing information for patients, practitioners, researchers, Industry and as a contact point for National and European patient associations. The idea is to gather forces at the European level in order to implement actions to leverage hurdles to the development of this powerful radionuclide and to identify pathologies in which it will be particularly relevant. A special emphasis will be given to train a new generation of young researchers and PhD students, promoting interdisciplinary competencies through international and inter-sectoral mobility. The long-term goal of this project is to make Astatine-211 technology available to all European citizen

La vallée de Saint-Rivoal : un paysage au gré des hommes

The Saint-Rivoal Valley : A Human Landscape In the Arrée Mountains (Britanny, France), the bocage has been conserved untouched. After clearing and then tilling the land, the people who settled in this area conserved a landscape that provides evidence of the material and social conditions with which they had to deal. Deeds, liege and land registries can be used to stratigraphically interpret and analyze the constitution of this landscape and to fix certain points in the gradual division of the land, sometimes only after the 17th century. Setting up, around the "ecological museum" in the Arrée Mountains (Regional Park of Armorica), a center for interpreting the landscape should make it possible to conduct experiments for dynamically conserving this heritage.En Bretagne, au cœur des monts d'Arrée, les éléments du paysage de bocage ont été conservés intacts. Tour à tour défricheurs puis agriculteurs, ceux qui ont occupé l'espace ont conduit jusqu'à nous un paysage qui témoigne des contraintes, tant matérielles que sociales, qui y ont été vécues et assumées. Les actes de partage, les aveux, les plans cadastraux nous permettent de le lire en stratigraphie, d'en analyser la constitution, de situer en certains points la fixation progressive du parcellaire, parfois seulement après le XVIIe siècle. La mise en place autour de l'écomusée des monts d'Arrée (Parc naturel régional d'Armorique) d'un centre d'interprétation du paysage devrait permettre de mener des expériences de conservation dynamique du patrimoine.Gestin Françoise. La vallée de Saint-Rivoal : un paysage au gré des hommes. In: Études rurales, n°121-124, 1991. De l'agricole au paysage. pp. 73-89

La fièvre du petit enfant : que font les parents? (à propos d'une enquête réalisée aux urgences pédiatriques de Brest en décembre 2000)

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Targeted alpha-therapy with 211At-anti-mCD138 mAb in a syngeneic murine Multiple Myeloma model : can repeated doses or fractionation protocol overpass single dose efficiency?

International audienc

Efficacy of Astatine-211 radioimmunotherapy of Multiple Myeloma using an anti-mCD138 monoclonal antibody in a syngeneic murine model

Abstracts of Annual Congress of the European Association of Nuclear Medicine October 13 – 17, 2018 Düsseldorf, GermanyInternational audienceAim: Multiple myeloma is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow. In spite of a very active search for new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) is a new cancer treatment modality with tumour specific antibodies coupled to alpha particle-emitting radionuclides. CD138 (Syndecan-1) is found mainly in epithelial cells, but was shown to be expressed by most myeloma cells, both in human and in the mouse. The aim of the study was to evaluate the biodistribution, toxicity and efficacy of a rat Astatin-211-labelled anti-mouse CD138 antibody (211At-9E7.4) in a syngeneic mouse myeloma model. Materials and methods: C57BL/KaLwRij mice were grafted with 106 5T33 cells (murine myeloma cell line). Biodistribution was studied 15 min, 1h, 4h, 7h, 14h and 21h post-administration of 211At- 9E7.4 mAb. Toxicity (animal weight, blood cell counts and transaminase) and RIT efficacy were studied after a dose escalation using 370, 555, 740 and 1110 kBq of 211At-9E7.4 and two control groups 211At-IgG2a isotype control at 555 kBq or no treatment, 10 days after tumour engraftment. Results: Studies demonstrated a highly statistical survival benefit for the mice treated with 211At-9E7.4 at 555 kBq (p=0,0006) and 740 kBq (p<0,0001). At 555 kBq, the survival median was increase by 34 days and at 740 kBq 65% of the mice survived 160 days after engraftment. For treatments with 370 kBq with 211At-9E7.4 or 211At-isotype control at 555 kBq no significant benefit was observed. The higher activity with 1110 kBq of 211At-9E7.4 was clearly radiotoxic since mice were euthanized after a lost more than 30% of baseline weight 14 days after radiopharmaceutical injection. For the other groups, except transient decreases of leukocytes and red cells, no other toxicity could be demonstrated, especially on liver function, which does not seem to be affected. Concerning red blood cells, the effect is much weaker than that observed with the use of Bismuth-213 at an injected activity of 3.7 MBq. Conclusions: RIT of MM using Astatine-211 coupled to monoclonal antibody directed against murine CD138 is effective. The activity in astate-211 which allows 60% survival corresponds to an activity injected in Bismuth-213 located between 3.7 and 7.4 MBq, which seems to reflect the influence of the half life of the two radionuclides. In addition, the upper half-life of astatine appears to be a benefit, particularly because of the lower toxicity observed in this syngeneic model of MM