RESUMO
The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.
Assuntos
Didesoxinucleosídeos/administração & dosagem , Monitoramento de Medicamentos/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Animais , Avaliação Pré-Clínica de MedicamentosRESUMO
MOON (Mediterranean Operational Oceanography Network http://www.moon-oceanforecasting.eu) provides near-real-time information on oil-spill detection (ocean color and SAR) and predictions [ocean forecasts (MFS and CYCOFOS) and oil-spill predictions (MEDSLIK)]. We employ this system to study the Lebanese oil-pollution crisis in summer 2006 and thus to assist regional and local decision makers in Europe, regionally and locally. The MEDSLIK oil-spill predictions obtained using CYCOFOS high-resolution ocean fields are compared with those obtained using lower-resolution MFS hydrodynamics, and both are validated against satellite observations. The predicted beached oil distributions along the Lebanese and Syrian coasts are compared with in situ observations. The oil-spill predictions are able to simulate the northward movement of the oil spill, with the CYCOFOS predictions being in better agreement with satellite observations. Among the free MEDSLIK parameters tested in the sensitivity experiments, the drift factor appears to be the most relevant to improve the quality of the results.