Comparaison de deux techniques de pré-purification des éluats de 68GA pour le marquage de peptides par automate de synthèse

National audienceObjectifs.–Le but de ce travail est d’évaluer, à travers différents essais cliniquesd’imagerie au68Ga en cours à Nantes, deux techniques de pré-purification deséluat de68Ga pour le marquage de peptides (DOTANOC et IMP288).Patients et méthodes.–Les deux techniques sont automatisées avec les appa-reils Eckert et Ziegler Modular-Lab PharmTracer®et Standard®. La technique1 consiste à fixer le68Ga issu du générateur sur une colonne échangeuse decations type STRATA-XC, pour récupérer une solution concentrée de68Ga dansle réacteur avec un mélange acétone/HCl 0,02 N. La technique 2 consiste à fixerle68Ga sur une colonne échangeuse de cations type Bond Elut-SCX, éluée avecun mélange concentré NaCl 5 M/HCl 0,1 N. Le radiomarquage de peptide avecla méthode 1 est réalisé en tampon acétate 0,2 M pH 4. Avec la méthode 2, ilest réalisé en tampon acétate 0,3 M pH 4,5 pour obtenir un pH final de 4. Lessolutions radiomarquées sont ensuite purifiées en ligne à l’aide de cartouchesde type Sep-Pack C18.Résultats.–Seule la technique 1 a été utilisée dans l’essai EUDRACT 2011-003542-40 (DOTANOC-68Ga) car disponible full GMP. Quelle que soit latechnique utilisée, les rendements de marquage se sont révélés acceptableset compris entre 60 et 80 %. Pour les essais EUDRACT 2011-005430-19 etEUDRACT 2011-002588-76 qui impliquent un peptide hydrophile (IMP 288),la technique 1 ne permet pas l’utilisation du système de purification etnécessite l’utilisation d’une quantité de peptide adaptée pour obtenir direc-tement une pureté radiochimique (PRC) > 90 % avec des activités spécifiques(AS) 80 MBq/nmoL et une PRC > 95 %.Conclusions.–La technique 1 bénéficie d’une méthode automatisée GMPmais ne permet pas la purification finale des peptides hydrophiles nid’atteindre des activités spécifiques élevées qui peuvent être obtenues avec latechnique 2

How to Simplify Tools for Natural Grassland Characterisation Based on Biological Measures Without Losing Too Much Information?

In marginal areas, such as the Pyrenees, natural grasslands are the only available resource for livestock feeding. Despite this, there is a lack of simple and efficient tools for advisers to aid the management of the complex vegetation of these grasslands. Therefore, we tested an approach derived from functional ecology, to construct such tools: using biological traits to inform on the agronomic characteristics and the way farmers’ practices act on them (Ansquer et al., 2004). Nevertheless, the required protocol of measurement is still time-consuming and difficult. In this paper, we test different ways of simplifying this protocol by reducing the number of species measured and not considering specific abundances

A Herbage Growth Model for Different Types of Natural Grassland

The aim of this work was to extend existing growth models established for pure stands to a wide range of grassland communities. For this purpose we built a simple growth model, including sub-models for radiation interception and use. Parameters for the effect of nutrient rates (N, P) and defoliation regimes were based on a plant trait database. Senescence and reproductive processes were particularly considered because of their importance in late spring growth. The model makes it possible to simulate the daily biomass production as a function of both environmental factors and the functional type of the dominant species in the community

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Are Leaf Traits Stable Enough to Rank Native Grasses in Contrasting Growth Conditions?

The growing interest in classifying species in response groups relating to variations in environmental factors has triggered the search for functional traits that express differences in ecological behaviour among plant species (Lavorel & Garnier, 2002). Specific leaf area (SLA) and leaf dry matter content (LDMC) reflect a fundamental trade-off in plant functioning between a fast growth rate (high SLA, low LDMC species) and nutrient conservation (low SLA, high LDMC species). This study aimed to analyse the stability of ranking native grasses by SLA and LDMC values under different plant growing conditions

Managing the Reproductive Development of Grasses by Grazing Practices

Grazing natural grassland communities is necessary for both productive (feeding herbivores) and environmental (maintenance of open landscapes) objectives. Management guidelines should take into account the functional diversity of plant species between and within grassland communities. The management of the heading stage of grasses by grazing is an important tool to maintain acceptable forage quality and to avoid the seeding of low-valued species. The heading stage should be managed even in extensive systems and this needs a good knowledge of the phenological development of dominant species. In this work we illustrate the approach through the study of the development of four contrasting grasses and analysing the consequences for grazing management. This work concerned only diversity of the plant components of the grassland ecosystem

Variation of LDMC and SLA Relationship Between Growth Forms in Natural Grasslands

In agro-ecological studies, there is a growing interest in measuring both leaf dry matter content (LDMC) and specific leaf area (SLA). This interest lies on the fact that leaf traits are linked to gradients of environmental factors and ecosystem functions. Working with three contrasting wild species, Garnier et al. (2001) proposed a model linking these two traits. The model shows a relatively simple non linear and negative correlation between LDMC and SLA. Nevertheless, none of the species used to build the model were grasses (GRA) or forb rosettes (ROS = i.e. dicotyledonous with large entire leaves and absence of stem at the vegetative stage); the species which make the largest contribution to the standing biomass of most natural grasslands. Furthermore, due to the divergent range of LDMC (and not SLA) values between these growth forms, Cruz et al. (2002) proposed that grass records alone could be used as an indicator of fertility gradients. The aim of this paper was to analyse discrepancies in the LDMC - SLA correlation with respect to model predictions in order to consider them in any development of LDMC-based tools for the management of natural vegetation

Survival in Norwegian BRCA1 mutation carriers with breast cancer

Several studies of survival in women with BRCA1 mutations have shown either reduced survival or no difference compared to controls. Programmes for early detection and treatment of inherited breast cancer, have failed to demonstrate a significant improvement in survival in BRCA1 mutation carriers