Uptake of 18F-fluorocholine, 18F-fluoro-ethyl- L -tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat

Introduction: The positron emission tomography (PET) tracers 18F-fluoro-ethyl-L-tyrosine (FET), 18F-fluorocholine (N,N-dimethyl-N-[18F]fluoromethyl-2-hydroxyethylammonium (FCH]) and 18F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study. Methods: F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD. Results: The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19±0.86 (1.32±0.26), 2.98±0.58 (0.51±0.11) and 11.02±3.84 (4.76±1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG). Conclusion: MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injurie

Genetic and environmental effects on crop development determining adaptation and yield

Slafer, Gustavo Ariel. ICREA - AGROTECNIO - Spain.Kantolic, Adriana Graciela. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Appendino, María Laura. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Tranquilli, Gabriela Edith. Instituto Nacional de Tecnología Agropecuaria (INTA). Recursos Naturales. Instituto de Recursos Biológicos. Buenos Aires, Argentina.Miralles, Daniel Julio. Universidad de Buenos Aires. Facultad de Agronomía. Buenos Aires, Argentina.Savin, Roxana. ICREA - AGROTECNIO - Spain.Crop development is a sequence of phenological events controlled by the genetic background and influenced by external factors, which determines changes in the morphology and/or function of organs (Landsberg, 1977). Although development is a continuous process, the ontogeny of a crop is frequently divided into discrete periods, for instance ‘vegetative’, ‘reproductive’ and ‘grain - filling’ phases (Slafer, 2012). Patterns of phenological development largely determine the adaptation of a crop to a certain range of environments. For example, genetic improvement in grain yield of wheat has been associated with shorter time from sowing to anthesis in Mediterranean environments of western Australia (Siddique et al., 1989), whereas no consistent trends in phenology were found where drought is present but not necessarily terminal, including environments of Argentina, Canada and the USA (Slafer and Andrade, 1989, 1993; Slafer et al., 1994a) (Fig. 12.1). Even in agricultural lands of the Mediterranean Basin where wheat has been grown for many centuries, breeding during the last century did not clearly change phenological patterns (Acreche et al., 2008). This chapter focuses on two major morphologically and hysiologically contrasting grain crops: wheat and soybean. For both species, we have an advanced understanding of development and physiology in general. Wheat is a determinate, long-day grass of temperate origin, which is responsive to vernalization. Soybean is a typically indeterminate (but with determinate intermediate variants), short-day grain legume of tropical origin, which is insensitive to vernalization. Comparisons with other species are used to highlight the similarities and differences. The aims of this chapter are to outline the developmental characteristics of grain crops and the links between phenology and yield, to revise the mechanisms of environmental and genetic control of development and to explore the possibilities of improving crop adaptation and yield potential through the fine-tuning of developmental patterns

Uptake of 18F-fluorocholine, 18F-fluoro-ethyl-L-tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat

Introduction: The positron emission tomography (PET) tracers 18F-fluoro-ethyl-L-tyrosine (FET), 18F-fluorocholine (N,N-dimethyl-N-[18F]fluoromethyl-2-hydroxyethylammonium (FCH]) and 18F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study. Methods: F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD. Results: The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19±0.86 (1.32±0.26), 2.98±0.58 (0.51±0.11) and 11.02±3.84 (4.76±1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG). Conclusion: MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injurie

Uptake of 18F-fluorocholine, 18F-fluoroethyl-l-tyrosine, and 18F-FDG in acute cerebral radiation injury in the rat : implications for separation of radiation necrosis from tumor recurrence

Differentiation between posttherapy radiation necrosis and recurrent tumor in humans with brain tumor is still a difficult diagnostic task. The new PET tracers 18F-fluoro-ethyl-l-tyrosine (FET) and 18F-fluorocholine (N,N-dimethyl-N-18F-fluoromethyl-2-hydroxyethylammonium [FCH]) have shown promise for improving diagnostic accuracy. This study assessed uptake of these tracers in experimental radiation injury. Methods: In a first model, circumscribed lesions were induced in the cortex of 35 rats using proton irradiation of 150 or 250 Gy. After radiation injury developed, uptake of 18F-FET, 18F-FCH, and 18F-FDG was measured using autoradiography and correlated with histology and disruption of the blood-brain barrier as determined with Evans blue. In a second model, uptake of the tracers was assessed in acute cryolesions, which are characterized by the absence of inflammatory cells. Results: Mean 18F-FET, 18F-FCH, and 18F-FDG standardized uptake values in the most active part of the radiation lesion and the contralateral normal cortex (in parentheses) were 2.27 ± 0.46 (1.42 ± 0.23), 2.52 ± 0.42 (0.61 ± 0.12), and 6.21 ± 1.19 (4.35 ± 0.47). The degree of uptake of 18F-FCH and 18F-FDG correlated with the density of macrophages. In cryolesions, 18F-FET uptake was similar to that in radiation lesions, and 18F-FCH uptake was significantly reduced. Conclusion: Comparison of tracer accumulation in cryolesions and radiation injuries demonstrates that 18F-FET uptake is most likely due to a disruption of the blood-brain barrier alone, whereas 18F-FCH is additionally trapped by macrophages. Uptake of both tracers in the radiation injuries is generally lower than the published uptake in tumors, suggesting that 18F-FET and 18F-FCH are promising tracers for separating radiation necrosis from tumor recurrence. However, the comparability of our data with the literature is limited by factors such as different species and acquisition protocols and modalities. Thus, more studies are needed to settle this issue. Nevertheless, 18F-FCH and 18F-FET seem superior to 18F-FDG for this purpose

Consistent model reduction of polymer chains in solution in dissipative particle dynamics: Model description

We introduce a framework for model reduction of polymer chain models for dissipative particle dynamics (DPD) simulations, where the properties governing the phase equilibria such as the characteristic size of the chain, compressibility, density, and temperature are preserved. The proposed methodology reduces the number of degrees of freedom required in traditional DPD representations to model equilibrium properties of systems with complex molecules (e.g. linear polymers). Based on geometrical considerations we explicitly account for the correlation between beads in fine-grained DPD models and consistently represent the effect of these correlations in a reduced model, in a practical and simple fashion via power laws and the consistent scaling of the simulation parameters. In order to satisfy the geometrical constraints in the reduced model we introduce bond–angle potentials that account for the changes in the chain free energy after the model reduction. Following this coarse-graining process we represent high molecular weight DPD chains (i.e. ≥200 beads per chain) with a significant reduction in the number of particles required (i.e. ≥20 times the original system). We show that our methodology has potential applications modeling systems of high molecular weight molecules at large scales, such as diblock copolymer and DNA

Cemiplimab for locally advanced and metastatic cutaneous squamous-cell carcinomas: Real-life experience from the French CAREPI study group

International audienceAlthough cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients